Seminars in Nephrology
Volume 30, Issue 4 , Pages 374-386 , July 2010

Congenital Anomalies of Kidney and Urinary Tract

  • Hakan R. Toka, MD, PhD

      Affiliations

    • Renal Division, Brigham and Women's Hospital, Boston, MA
    • Corresponding Author InformationAddress reprint requests to Hakan R. Toka, MD, PhD, Brigham and Women's Hospital/Harvard Institute of Medicine, HIM # 534, 4 Blackfan Circle, Boston, MA 02115
    • ,
  • Okan Toka, MD

      Affiliations

    • Department of Pediatrics, Friedrich-Alexander University, Erlangen-Nuremberg, Germany
    • ,
  • Ali Hariri, MD

      Affiliations

    • Department of Nephrology, Internal Medicine and Scientific Affairs, Takeda Pharmaceuticals of North America, Deerfield, IL
    • ,
  • Hiep T. Nguyen, MD

      Affiliations

    • Department of Urology, Children's Hospital Boston, Boston, MA

References 

  1. Port FK. Morbidity and mortality in dialysis patients. Kidney Int. 1994;46:1728–1737
  2. Dziarmaga A, Quinlan J, Goodyer P. Renal hypoplasia: lessons from Pax2. Pediatr Nephrol. 2006;21:26–31
  3. Lewis MA, Shaw J, Sinha M, et al. UK Renal Registry 11th Annual Report (December 2008): chapter 13 demography of the UK paediatric renal replacement therapy population. Nephron Clin Pract. 2009;111:c257–c267
  4. Schedl A. Renal abnormalities and their developmental origin. Nat Rev Genet. 2007;8:791–802
  5. Kerecuk L, Schreuder MF, Woolf AS. Renal tract malformations: perspectives for nephrologists. Nat Clin Pract Nephrol. 2008;4:312–325
  6. Carlson BM. Human embryology and developmental biology. CV Mosby; 1999;
  7. Potter EL. Normal and abnormal development of the kidney. The Kidney.
  8. Nyengaard JR, Bendtsen TF. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat Rec. 1992;232:194–201
  9. McMahon AP, Aronow BJ, Davidson DR, et al. GUDMAP: the genitourinary developmental molecular anatomy project. J Am Soc Nephrol. 2008;19:667
  10. Mishra A. Renal agenesis: report of an interesting case. Br J Radiol. 2007;80:e167
  11. Woolf AS, Hillman KA. Unilateral renal agenesis and the congenital solitary functioning kidney: developmental, genetic and clinical perspectives. BJU Int. 2007;99:17
  12. Rudolph CD, Rudolph AM, Hostetter MK, Lister GE, Siegel NJ. In: Rudolph's pediatrics. 21st ed.. McGraw-Hill Professional; 2002;p. 1638–1642
  13. Thorner P, Bernstein J, Landing BH. In: Kidney and lower urinary tract (Diseases of the fetus and newborn). 2nd ed.. London: Chapman and Hall Medical; 1995;p. 609–691
  14. Damen-Elias HAM, Stoutenbeek PH, Visser GHA, Nikkels PGJ, De Jong T. Concomitant anomalies in 100 children with unilateral multicystic kidney. Ultrasound Obstet Gynecol. 2005;25:384–388
  15. Huang WY, Peters CA, Zurakowski D, et al. Renal biopsy in congenital ureteropelvic junction obstruction: evidence for parenchymal maldevelopment. Kidney Int. 2006;69:137–143
  16. Gargollo PC, Diamond DA. Therapy insight: what nephrologists need to know about primary vesicoureteral reflux. Nat Clin Pract Nephrol. 2007;3:551
  17. Small MJ, Copel JA. Practical guidelines for diagnosing and treating fetal hydronephrosis. Contemporary Ob Gyn. 2004;49:59–77
  18. Ridson RA, Yeung CK, Ransley PG. Reflux nephropathy in children submitted to unilateral nephrectomy: a clinicopathological study. Clin Nephrol. 1993;40:308–314
  19. Mackie GG, Stephens FD. Duplex kidneys: a correlation of renal dysplasia with position of the ureteral orifice. J Urol. 1975;114:274
  20. Briggs CE, Guo CY, Schoettler C, et al. A genome scan in affected sib-pairs with familial vesicoureteral reflux identifies a locus on chromosome 5. Eur J Hum Genet. 2009;
  21. Weber S, Moriniere V, Knuppel T, et al. Prevalence of mutations in renal developmental genes in children with renal hypodysplasia: results of the ESCAPE study. J Am Soc Nephrol. 2006;17:2864
  22. Sanna-Cherchi S, Caridi G, Weng PL, et al. Genetic approaches to human renal agenesis/hypoplasia and dysplasia. Pediatr Nephrol. 2007;22:1675–1684
  23. McPherson E, Carey J, Kramer A, et al. Dominantly inherited renal adysplasia. Am J Med Genet. 1987;26:863–872
  24. Sanna-Cherchi S, Caridi G, Weng PL, et al. Localization of a gene for nonsyndromic renal hypodysplasia to chromosome 1p32-33. Am J Hum Genet. 2007;80:539–549
  25. Weng PL, Sanna-Cherchi S, Hensle T, et al. A recessive gene for primary vesicoureteral reflux maps to chromosome 12p11-q13. J Am Soc Nephrol. 2009;20:1633
  26. Ogata T, Muroya K, Sasagawa I, et al. Genetic evidence for a novel gene(s) involved in urogenital development on 10q26. Kidney Int. 2000;58:2281–2290
  27. Vats AN, Ishwad C, Vats KR, et al. Steroid-resistant nephrotic syndrome and congenital anomalies of kidneys: evidence of locus on chromosome 13q. Kidney Int. 2003;64:17–24
  28. Vats KR, Ishwad C, Singla I, et al. A locus for renal malformations including vesico-ureteric reflux on chromosome 13q33-34. J Am Soc Nephrol. 2006;17:1158
  29. Chambers JC, Elliott P, Zabaneh D, et al. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet. 2008;40:716–718
  30. Amos CI, Wu X, Broderick P, et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25. 1. Nat Genet. 2008;40:616
  31. Garshasbi M, Motazacker MM, Kahrizi K, et al. SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly. Hum Genet. 2006;118:708–715
  32. Komatsu A, Nagasaki K, Fujimori M, Amano J, Miki Y. Identification of novel deletion polymorphisms in breast cancer. Int J Oncol. 2008;33:261
  33. Stanczak CM, Chen Z, Zhang YH, Nelson SF, McCabe ER. Deletion mapping in Xp21 for patients with complex glycerol kinase deficiency using SNP mapping arrays. Hum Mutat. 2007;28:235
  34. Zweier C, Peippo MM, Hoyer J, et al. Haploinsufficiency of TCF4 causes syndromal mental retardation with intermittent hyperventilation (Pitt-Hopkins syndrome). Am J Hum Genet. 2007;80:994–1001
  35. Vissers L, van Ravenswaaij CMA, Admiraal R, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004;36:955–957
  36. Ng SB, Turner EH, Robertson PD, et al. Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009;461:272–276
  37. Choi M, Scholl UI, Ji W, et al. Genetic diagnosis by whole exome capture and massively parallel DNA sequencing. Proc Natl Acad Sci U S A. 2009;106:19096–19101
  38. Siva N. 1000 Genomes project. Nat Biotechnol. 2008;26:256
  39. Tabatabaeifar M, Schlingmann KP, Litwin M, et al. Functional analysis of BMP4 mutations identified in pediatric CAKUT patients. Pediatr Nephrol. 2009;24:1–8
  40. Stankovi A, Živkovi M, Kosti M, et al. Expression profiling of the AT2R mRNA in affected tissue from children with CAKUT. Clin Biochem. 2009;
  41. Wiesel A, Queisser-Luft A, Clementi M, Bianca S, Stoll C. Prenatal detection of congenital renal malformations by fetal ultrasonographic examination: an analysis of 709,030 births in 12 European countries. Eur J Med Genet. 2005;48:131–144
  42. Hill LM, Nowak A, Hartle R, Tush B. Fetal compensatory renal hypertrophy with a unilateral functioning kidney. Ultrasound Obstet Gynecol. 2000;15:191–193
  43. Winyard PJD, Nauta J, Lirenman DS, et al. Deregulation of cell survival in cystic and dysplastic renal development. Kidney Int. 1996;49:135–146
  44. Webb NJA, Lewis MA, Bruce J, et al. Unilateral multicystic dysplastic kidney: the case for nephrectomy. Br Med J. 1997;76:31
  45. Hodson CJ, Edwards D. Chronic pyelonephritis and vesico-ureteric reflux. Clin Radiol. 1960;11:219–231
  46. Woolf AS, Wilcox DT. Understanding primary vesicoureteric reflux and associated nephropathies. Curr Paediatr. 2004;14:563–567
  47. Silva JMP, Oliveira EA, Diniz JSS, et al. Gender and vesico-ureteral reflux: a multivariate analysis. Pediatr Nephrol. 2006;21:510–516
  48. Sidhu G, Beyene J, Rosenblum ND. Outcome of isolated antenatal hydronephrosis: a systematic review and meta-analysis. Pediatr Nephrol. 2006;21:218–224
  49. Dhundiraj KM, Madhukar DN, Ambadasrao PG, Wamanrao KS, Prem ZM. Potter's syndrome: a report of 5 cases. Ind J Pathol Microbiol. 2006;49:254
  50. Kupferman JC, Druschel CM, Kupchik GS. Increased prevalence of renal and urinary tract anomalies in children with Down syndrome. Pediatrics. 2009;124:e615
  51. Cromie WJ, Lee K, Houde K, Holmes L. Implications of prenatal ultrasound screening in the incidence of major genitourinary malformations. J Urol. 2001;165:1677–1680
  52. Clark TJ, Martin WL, Divakaran TG, et al. Prenatal bladder drainage in the management of fetal lower urinary tract obstruction: a systematic review and meta-analysis. Obstetr Gynecol. 2003;102:367
  53. Roth KS, Carter WH, Chan J. Obstructive nephropathy in children: long-term progression after relief of posterior urethral valve. Pediatrics. 2001;107:1004
  54. Duke V, Quinton R, Gordon I, Bouloux P, Woolf A. Proteinuria, hypertension and chronic renal failure in X-linked Kallmann's syndrome, a defined genetic cause of solitary functioning kidney. Nephrol Dial Transplant. 1998;13:1998–2003
  55. Kiprov DD, Colvin RB, McCluskey RT. Focal and segmental glomerulosclerosis and proteinuria associated with unilateral renal agenesis. Lab Invest. 1982;46:275
  56. Heinonen PK. Gestational hypertension and preeclampsia associated with unilateral renal agenesis in women with uterine malformations. Eur J Obstet Gynecol. 2004;114:39–43
  57. Gonz E, Guti E, Morales E, Hern E. Factors influencing the progression of renal damage in patients with unilateral renal agenesis and remnant kidney. Kidney Int. 2005;68:263–270
  58. Hostetter TH, Olson JL, Rennke HG, Venkatachalam MA, Brenner BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol Renal Physiol. 1981;241:85
  59. Sanna-Cherchi S, Ravani P, Corbani V, et al. Renal outcome in patients with congenital anomalies of the kidney and urinary tract. Kidney Int. 2009;76:528–533
  60. Wheeler DM, Vimalachandra D, Hodson EM, et al. Interventions for primary vesicoureteric reflux. Cochrane Database Syst Rev. 2004;3:CD001532
  61. Craig JC, PhD E, Irwig LM, et al. Does treatment of vesicoureteric reflux in childhood prevent end-stage renal disease attributable to reflux nephropathy?. Pediatrics. 2000;105:1236
  62. Ardissino G, Testa S, Dacco V, et al. Proteinuria as a predictor of disease progression in children with hypodysplastic nephropathy: data from the ItalKid Project. Pediatr Nephrol. 2004;19:172–177
  63. Neild GH, Thomson G, Nitsch D, et al. Renal outcome in adults with renal insufficiency and irregular asymmetric kidneys. BMC Nephrol. 2004;5:12
  64. Wühl E, Mehls O, Schaefer F. Antihypertensive and antiproteinuric efficacy of ramiprilin children with chronic renal failure. Kidney Int. 2004;66:768–776
  65. Ardissino G, Vigano S, Testa S, et al. No clear evidence of ACEi efficacy on the progression of chronic kidney disease in children with hypodysplastic nephropathy report from the ItalKid Project database. Nephrol Dial Transplant. 2007;22:2525
  66. Taranta A, Palma A, De Luca V, et al. Renal-coloboma syndrome: a single nucleotide deletion in the PAX2 gene at exon 8 is associated with a highly variable phenotype. Clin Nephrol. 2007;67:1
  67. Fletcher J, Hu M, Berman Y, et al. Multicystic dysplastic kidney and variable phenotype in a family with a novel deletion mutation of PAX2. J Am Soc Nephrol. 2005;16:2754
  68. Decramer S, Parant O, Beaufils S, et al. Anomalies of the TCF2 gene are the main cause of fetal bilateral hyperechogenic kidneys. J Am Soc Nephrol. 2007;18:923
  69. Nishimura H, Yerkes E, Hohenfellner K, et al. Role of the angiotensin type 2 receptor gene in congenital anomalies of the kidney and urinary tract, CAKUT, of mice and men. Mol Cell. 1999;3:1–10
  70. Weber S, Taylor JC, Winyard P, et al. SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol. 2008;19:891
  71. Dudley AT, Lyons KM, Robertson EJ. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev. 1995;9:2795
  72. Miyamoto N, Yoshida M, Kuratani S, Matsuo I, Aizawa S. Defects of urogenital development in mice lacking Emx2. Development. 1997;124:1653
  73. Dressler GR. Tubulogenesis in the developing mammalian kidney. Trends Cell Biol. 2002;12:390–395
  74. Perantoni AO, Timofeeva O, Naillat F, et al. Inactivation of FGF8 in early mesoderm reveals an essential role in kidney development. Development. 2005;132:3859
  75. Ohuchi H, Kimura S, Watamoto M, Itoh N. Involvement of fibroblast growth factor (FGF) 18-FGF8 signaling in specification of left-right asymmetry and brain and limb development of the chick embryo. Mech Dev. 2000;95:55–66
  76. Poladia DP, Kish K, Kutay B, et al. Role of fibroblast growth factor receptors 1 and 2 in the metanephric mesenchyme. Dev Biol. 2006;291:325–339
  77. Kume T, Deng K, Hogan BL. Murine forkhead/winged helix genes Foxc1 (Mf1) and Foxc2 (Mfh1) are required for the early organogenesis of the kidney and urinary tract. Development. 2000;127:1387
  78. Hatini V, Huh SO, Herzlinger D, Soares VC, Lai E. Essential role of stromal mesenchyme in kidney morphogenesis revealed by targeted disruption of Winged Helix transcription factor BF-2. Genes Dev. 1996;10:1467
  79. Esquela AF, Lee SJ. Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol. 2003;257:356–370
  80. Sanchez MP, Silos-Santiago I, Frisen J, He B, Lira SA, Barbacid M. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature. 1996;382:70–73
  81. Enomoto H, Araki T, Jackman A, et al. GFR alpha1-deficient mice have deficits in the enteric nervous system and kidneys. Neuron. 1998;21:317–324
  82. Michos O, Panman L, Vintersten K, et al. Gremlin-mediated BMP antagonism induces the epithelial-mesenchymal feedback signaling controlling metanephric kidney and limb organogenesis. Development. 2004;131:3401
  83. Davis AP, Witte DP, Hsieh-Li HM, Potter SS, Capecchi MR. Absence of radius and ulna in mice lacking hoxa-11 and hoxd-11. 1995;
  84. Wilson VA, Gallagher JT, Merry CLR. Heparan sulfate 2-O-sulfotransferase (Hs2st) and mouse development. Glycoconj J. 2002;19:347–354
  85. Müller U, Wang D, Denda S, et al. Integrin 8 1 is critically important for epithelial–mesenchymal interactions during kidney morphogenesis. Cell. 1997;88:603
  86. Reggiani L, Raciti D, Airik R. The prepattern transcription factor.
  87. Kreidberg JA, Donovan MJ, Goldstein SL, et al. Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis. Development. 1996;122:3537–3547
  88. Kobayashi A, Kwan KM, Carroll TJ, et al. Distinct and sequential tissue-specific activities of the LIM-class homeobox gene Lim1 for tubular morphogenesis during kidney development. Development. 2005;132:2809–2823
  89. Brandenberger R, Schmidt A, Linton J, et al. Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin {alpha} 8 {beta} 1 in the embryonic kidney. J Cell Biol. 2001;154:447
  90. James RG, Kamei CN, Wang Q, Jiang R, Schultheiss TM. Odd-skipped related 1 is required for development of the metanephric kidney and regulates formation and differentiation of kidney precursor cells. Development. 2006;133:2995
  91. Bouchard M, Souabni A, Mandler M, Neubüser A, Busslinger M. Nephric lineage specification by Pax2 and Pax8. Genes Dev. 2002;16:2958
  92. Schnabel CA, Godin RE, Cleary ML. Pbx1 regulates nephrogenesis and ureteric branching in the developing kidney. Dev Biol. 2003;254:262–276
  93. Kim D, Dressler GR. PTEN modulates GDNF/RET mediated chemotaxis and branching morphogenesis in the developing kidney. Dev Biol. 2007;307:290–299
  94. Nakai S, Sugitani Y, Sato H, et al. Crucial roles of Brn1 in distal tubule formation and function in mouse kidney. Development. 2003;130:4751
  95. Mendelsohn C, Lohnes D, Decimo D, et al. Function of the retinoic acid receptors (RARs) during development (II). Multiple abnormalities at various stages of organogenesis in RAR double mutants. Development. 1994;120:2749
  96. Niederreither K, Fraulob V, Garnier JM, Chambon P, Dollé P. Differential expression of retinoic acid-synthesizing (RALDH) enzymes during fetal development and organ differentiation in the mouse. Mech Dev. 2002;110:165–171
  97. Levinson R, Mendelsohn C. Stromal progenitors are important for patterning epithelial and mesenchymal cell types in the embryonic kidney. Semin Cell Dev Biol. 2003;14:225–231
  98. Attié-Bitach T, Abitbol M, Gerard M, et al. Expression of the RET proto-oncogene in human embryos. Am J Med Genet. 1998;80:481–486
  99. Schuchardt A, D'Agati V, Larsson-Blomberg L, Costantini F, Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. 1994;
  100. Kobayashi H, Kawakami K, Asashima M, Nishinakamura R. Six1 and Six4 are essential for Gdnf expression in the metanephric mesenchyme and ureteric bud formation, while Six1 deficiency alone causes mesonephric-tubule defects. Mech Dev. 2007;124:290–303
  101. Gai Z, Zhou G, Itoh S, et al. Trps1 functions downstream of Bmp7 in kidney development. J Am Soc Nephrol. 2009;
  102. Kitamoto Y, Tokunaga H, Tomita K. Vascular endothelial growth factor is an essential molecule for mouse kidney development: glomerulogenesis and nephrogenesis. J Clin Invest. 1997;99:2351
  103. Iglesias DM, Hueber PA, Chu LL, et al. Canonical WNT signaling during kidney development. Am J Physiol Renal Physiol. 2007;293:F494
  104. Carroll TJ, Park JS, Hayashi S, Majumdar A, McMahon AP. Wnt9b plays a central role in the regulation of mesenchymal to epithelial transitions underlying organogenesis of the mammalian urogenital system. Dev Cell. 2005;9:283–292
  105. Majumdar A, Vainio S, Kispert A, McMahon J, McMahon AP. Wnt11 and Ret/Gdnf pathways cooperate in regulating ureteric branching during metanephric kidney development. Development. 2003;130:3175

PII: S0270-9295(10)00096-3

doi: 10.1016/j.semnephrol.2010.06.004

Seminars in Nephrology
Volume 30, Issue 4 , Pages 374-386 , July 2010

Article Tools

* Image Usage & Resolution