Skip to main content

Advertisement

SpringerLink
Log in

Mechanisms of renal injury and progression of renal disease in congenital obstructive nephropathy

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Congenital obstructive nephropathy accounts for the greatest fraction of chronic kidney disease in children. Genetic and nongenetic factors responsible for the lesions are largely unidentified, and attention has been focused on minimizing obstructive renal injury and optimizing long-term outcomes. The cellular and molecular events responsible for obstructive injury to the developing kidney have been elucidated from animal models. These have revealed nephron loss through cellular phenotypic transition and cell death, leading to the formation of atubular glomeruli and tubular atrophy. Altered renal expression of growth factors and cytokines, including angiotensin, transforming growth factor-β, and adhesion molecules, modulate cell death by apoptosis or phenotypic transition of glomerular, tubular, and vascular cells. Mediators of cellular injury include hypoxia, ischemia, and reactive oxygen species, while fibroblasts undergo myofibroblast transformation with increased deposition of extracellular matrix. Progression of the lesions involves interstitial inflammation and interstitial fibrosis, both of which impair growth of the obstructed kidney and result in compensatory growth of the contralateral kidney. The long-term outcome depends on timing and severity of the obstruction and its relief, minimizing ongoing injury, and enhancing remodeling. Advances will depend on new biomarkers to evaluate the severity of obstruction, to determine therapy, and to follow the evolution of lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Chevalier RL, Peters CA (2003) Congenital urinary tract obstruction: Proceedings of the State-Of-The-Art Strategic Planning Workshop - National Institutes of Health, Bethesda, Maryland, USA, 11–12 March 2002. Pediatr Nephrol 18:576–606

    PubMed  Google Scholar 

  2. Airik R, Kispert A (2007) Down the tube of obstructive nephropathies: the importance of tissue interactions during ureter development. Kidney Int 72:1459–1467

    CAS  PubMed  Google Scholar 

  3. Miyazaki Y, Tsuchida S, Nishimura H, Pope JC, Harris RC, McKanna JM, Inagami T, Hogan BM, Fogo A, Ichikawa I (1998) Angiotensin induces the urinary peristaltic machinery during the perinatal period. J Clin Invest 102:1489–1497

    CAS  PubMed  Google Scholar 

  4. Miyazaki Y, Tsuchida S, Fogo A, Ichikawa I (1999) The renal lesions that develop in neonatal mice during angiotensin inhibition mimic obstructive nephropathy. Kidney Int 55:1683–1695

    CAS  PubMed  Google Scholar 

  5. Chang CP, McDill BW, Neilson JR, Joist HE, Epstein JA, Crabtree GR, Chen F (2004) Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery. J Clin Invest 113:1051–1058

    CAS  PubMed  Google Scholar 

  6. Pope JC, Brock JW III, Adams MC, Miyazaki Y, Stephens FD, Ichikawa I (2001) Congenital anomalies of the kidney and urinary tract—role of the loss of function mutation in the pluripotent angiotensin type 2 receptor gene. J Urol 165:196–202

    CAS  PubMed  Google Scholar 

  7. Hiraoka M, Taniguchi T, Nakai H, Kino M, Okada Y, Tanizawa A, Tsukahara H, Ohshima Y, Muramatsu I, Mayumi M (2001) No evidence for AT2R gene derangement in human urinary tract anomalies. Kidney Int 59:1244–1249

    CAS  PubMed  Google Scholar 

  8. Peters CA (1997) Obstruction of the fetal urinary tract. J Am Soc Nephrol 8:653–663

    CAS  PubMed  Google Scholar 

  9. Matsell DG, Tarantal AF (2002) Experimental models of fetal obstructive nephropathy. Pediatr Nephrol 17:470–476

    PubMed  Google Scholar 

  10. Peters CA, Carr MC, Lais A, Retik AB, Mandell J (1992) The response of the fetal kidney to obstruction. J Urol 148:503–509

    CAS  PubMed  Google Scholar 

  11. Matsell DG, Mok A, Tarantal AF (2002) Altered primate glomerular development due to in utero-urinary tract obstruction. Kidney Int 61:1263–1269

    PubMed  Google Scholar 

  12. MacDonald MS, Emery JL (1959) The late intrauterine and postnatal development of human renal glomeruli. J Anat 93:331–340

    CAS  PubMed  Google Scholar 

  13. Larsson L, Aperia A, Wilton P (1980) Effect of normal development on compensatory renal growth. Kidney Int 18:29–35

    CAS  PubMed  Google Scholar 

  14. Gilbert T, Lelievre-Pegorier M, Malienou R, Meulemans A, Merlet-Benichou C (1987) Effects of prenatal and postnatal exposure to gentamicin on renal differentiation in the rat. Toxicology 43:301–313

    CAS  PubMed  Google Scholar 

  15. Hartman HA, Lai HL, Patterson P (2007) Cessation of renal morphogenesis in mice. Dev Biol 310:379–387

    CAS  PubMed  Google Scholar 

  16. Chevalier RL, Forbes MS, Thornhill BA (2009) Ureteral obstruction as a model of renal interstitial fibrosis and obstructive nephropathy. Kidney Int 75:1145–1152

    PubMed  Google Scholar 

  17. Larsson L, Maunsbach AB (1980) The ultrastructural development of the glomerular filtration barrier in the rat kidney: a morphometric analysis. J Ultrastr Res 72:392–406

    CAS  Google Scholar 

  18. Chevalier RL, Kim A, Thornhill BA, Wolstenholme JT (1999) Recovery following relief of unilateral ureteral obstruction in the neonatal rat. Kidney Int 55:793–807

    CAS  PubMed  Google Scholar 

  19. Hilgers KF, Nagaraj SK, Karginova EA, Kazakova IG, Chevalier RL, Carey RM, Pentz ES, Gomez RA (1998) Molecular cloning of KS, a novel rat gene expressed exclusively in the kidney. Kidney Int 54:1444–1454

    CAS  PubMed  Google Scholar 

  20. Poucell-Hatton S, Huang M, Bannykh S, Benirschke K, Masliah E (2000) Fetal obstructive uropathy: patterns of renal pathology. Pediatr Dev Pathol 3:223–231

    CAS  PubMed  Google Scholar 

  21. Tarantal AF, Han VKM, Cochrum KC, Mok A, DaSilva M, Matsell DG (2001) Fetal rhesus monkey model of obstructive renal dysplasia. Kidney Int 59:446–456

    CAS  PubMed  Google Scholar 

  22. Chevalier RL, Chung KH, Smith CD, Ficenec M, Gomez RA (1996) Renal apoptosis and clusterin following ureteral obstruction: the role of maturation. J Urol 156:1474–1479

    CAS  PubMed  Google Scholar 

  23. Cachat F, Lange-Sperandio B, Chang AY, Kiley SC, Thornhill BA, Forbes MS, Chevalier RL (2003) Ureteral obstruction in neonatal mice elicits segment-specific tubular cell responses leading to nephron loss. Kidney Int 63:564–575

    PubMed  Google Scholar 

  24. Thornhill BA, Burt LA, Chen C, Forbes MS, Chevalier RL (2005) Variable chronic partial ureteral obstruction in the neonatal rat: a new model of ureteropelvic junction obstruction. Kidney Int 67:42–52

    PubMed  Google Scholar 

  25. Chevalier RL, Thornhill BA, Wolstenholme JT, Kim A (1999) Unilateral ureteral obstruction in early development alters renal growth: dependence on the duration of obstruction. J Urol 161:309–313

    CAS  PubMed  Google Scholar 

  26. Peters CA, Gaertner RC, Carr MC, Mandell J (1993) Fetal compensatory renal growth due to unilateral ureteral obstruction. J Urol 150:597–600

    CAS  PubMed  Google Scholar 

  27. Yoo KH, Thornhill BA, Forbes MS, Chevalier RL (2006) Compensatory renal growth due to neonatal ureteral obstruction: implications for clinical studies. Pediatr Nephrol 21:368–375

    PubMed  Google Scholar 

  28. Gasser B, Mauss Y, Ghnassia JP, Favre R, Kohler M, Yu O, Vonesch JL (1993) A quantitative study of normal nephrogenesis in the human fetus: its implication in the natural history of kidney changes due to low obstructive uropathies. Fetal Diagn Ther 8:371–384

    CAS  PubMed  Google Scholar 

  29. Rosen S, McClellan D, Huang WY, Borer J, Peters C (2003) The morphology of the kidney in ureteropelvic junction obstruction (abstract). Pediatr Nephrol 18:586–587

    Google Scholar 

  30. Snyder HM, Lebowitz RL, Colodny AH, Bauer SB, Retik AB (1980) Ureteropelvic junction obstruction in children. Urol Clin North Am 7:273–290

    PubMed  Google Scholar 

  31. Valayer J, Adda G (1982) Hydronephrosis due to pelviureteric junction obstruction in infancy. Brit J Urol 54:451–454

    CAS  PubMed  Google Scholar 

  32. Eskild-Jensen A, Frokiaer J, Djurhuus JC, Jorgensen TM, Nyengaard JR (2002) Reduced number of glomeruli in kidneys with neonatally induced partial ureteropelvic obstruction in pigs. J Urol 167:1435–1439

    PubMed  Google Scholar 

  33. Josephson S (1983) Experimental obstructive hydronephrosis in newborn rats: III. long-term effects on renal function. J Urol 129:396–400

    CAS  PubMed  Google Scholar 

  34. Chevalier RL, Thornhill BA, Chang AY, Cachat F, Lackey A (2002) Recovery from release of ureteral obstruction in the rat: relationship to nephrogenesis. Kidney Int 61:2033–2043

    PubMed  Google Scholar 

  35. Thornhill BA, Forbes MS, Marcinko ES, Chevalier RL (2007) Glomerulotubular disconnection in neonatal mice after relief of partial ureteral obstruction. Kidney Int 72:1103–1112

    CAS  PubMed  Google Scholar 

  36. Garcia CH, Krueger K, Landing BH, Wells TR (1986) Microdissection demonstration of the lesion of the endocrine kidney in children. Pediatr Pathol 5:45–54

    CAS  PubMed  Google Scholar 

  37. Konda R, Orikasa S, Sakai K, Ota S, Kimura N (1996) The distribution of renin containing cells in scarred kidneys. J Urol 156:1450–1454

    CAS  PubMed  Google Scholar 

  38. Chevalier RL, Forbes MS (2008) Generation and evolution of atubular glomeruli in the progression of renal disorders. J Am Soc Nephrol 19:197–206

    PubMed  Google Scholar 

  39. Chevalier RL (2006) Obstructive nephropathy: towards biomarker discovery and gene therapy. Nat Clin Prac Nephrol 2:157–168

    CAS  Google Scholar 

  40. Huang WY, Peters CA, Zurakowski D, Borer JG, Diamond DA, Bauer SB, McLellan DL, Rosen S (2006) Renal biopsy in congenital ureteropelvic junction obstruction: evidence for parenchymal maldevelopment. Kidney Int 69:137–143

    PubMed  Google Scholar 

  41. Miyajima A, Chen J, Lawrence C, Ledbetter S, Soslow RA, Stern J, Jha S, Pigato J, Lemer ML, Poppas DP, Vaughan ED Jr, Felsen D (2000) Antibody to transforming growth factor-β ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int 58:2301–2313

    CAS  PubMed  Google Scholar 

  42. Misseri R, Meldrum DR, Dinarello CA, Dagher P, Hile KL, Rink RC, Meldrum KK (2005) TNF-alpha mediates obstruction-induced renal tubular cell apoptosis and proapoptotic signaling. Am J Physiol Renal Physiol 288:F406–F411

    CAS  PubMed  Google Scholar 

  43. Hughes J, Johnson RJ (1999) Role of Fas (CD95) in tubulointerstitial disease induced by unilateral ureteric obstruction. Am J Physiol 277:F26–F32

    CAS  PubMed  Google Scholar 

  44. Choi YJ, Mendoza L, Rha SJ, Sheikh-Hamad D, Baranowska-Daca E, Nguyen V, Smith CW, Nassar G, Suki WN, Truong LD (2001) Role of p53-dependent activation of caspases in chronic obstructive uropathy: evidence from p53 null mutant mice. J Am Soc Nephrol 12:983–992

    CAS  PubMed  Google Scholar 

  45. Malik RK, Thornhill BA, Chang AY, Kiley SC, Chevalier RL (2001) Renal apoptosis parallels ceramide content following chronic ureteral obstruction in the neonatal rat. Am J Physiol 281:F56–F61

    CAS  Google Scholar 

  46. Chung KH, Chevalier RL (1996) Arrested development of the neonatal kidney following chronic ureteral obstruction. J Urol 155:1139–1144

    CAS  PubMed  Google Scholar 

  47. Burt LE, Forbes MS, Thornhill BA, Chevalier RL (2007) Renal vascular endothelial growth factor (VEGF) in neonatal obstructive nephropathy: I. Endogenous VEGF. Am J Physiol 292:F158–F167

    CAS  Google Scholar 

  48. Silverstein DM, Travis BR, Thornhill BA, Schurr JS, Kolls JK, Leung JC, Chevalier RL (2003) Altered expression of immune modulator and structural genes in neonatal unilateral ureteral obstruction. Kidney Int 64:25–35

    CAS  PubMed  Google Scholar 

  49. Forbes MS, Thornhill BA, Park MH, Chevalier RL (2007) Lack of endothelial nitric-oxide synthase leads to progressive focal renal injury. Am J Pathol 170:87–99

    CAS  PubMed  Google Scholar 

  50. Murer L, Benetti E, Centi S, Della VM, Artifoni L, Capizzi A, Zucchetta P, Del PD, Carasi C, Montini G, Rigamonti W, Zaccello G (2006) Clinical and molecular markers of chronic interstitial nephropathy in congenital unilateral ureteropelvic junction obstruction. J Urol 176:2668–2673

    CAS  PubMed  Google Scholar 

  51. Han SW, Lee SE, Kim JH, Jeong HJ, Rha KH, Choi SK (1998) Does delayed operation for pediatric ureteropelvic junction obstruction cause histopathological changes? J Urol 160:984–988

    CAS  PubMed  Google Scholar 

  52. Valles P, Pascual L, Manucha W, Carrizo L, Ruttler M (2003) Role of endogenous nitric oxide in unilateral ureteropelvic junction obstruction in children. Kidney Int 63:1104–1115

    CAS  PubMed  Google Scholar 

  53. Ward RM, Starr NT, Snow BW, Bellinger MF, Pysher TJ, Zaino RJ (1989) Serial renal function in an ovine model of unilateral fetal urinary tract obstruction. J Urol 142:652–656

    CAS  PubMed  Google Scholar 

  54. Chevalier RL (1984) Chronic partial ureteral obstruction in the neonatal guinea pig. II: pressure gradients affecting glomerular filtration rate. Pediatr Res 18:1271–1277

    CAS  PubMed  Google Scholar 

  55. Lama G, Ferraraccio F, Iaccarino F, Luongo I, Marte A, Rambaldi PF, Esposito-Salsano M (2003) Pelviureteral junction obstruction: correlation of renal cell apoptosis and differential renal function. J Urol 169:2335–2338

    PubMed  Google Scholar 

  56. Winyard PJD, Nauta J, Lirenman DS, Hardman P, Sams VR, Risdon RA, Woolf AS (1996) Deregulation of cell survival in cystic and dysplastic renal development. Kidney Int 49:135–146

    CAS  PubMed  Google Scholar 

  57. Kiley SC, Thornhill BA, Tang SS, Ingelfinger JR, Chevalier RL (2003) Growth factor-mediated phosphorylation of proapoptotic BAD reduces tubule cell death in vitro and in vivo. Kidney Int 63:33–42

    CAS  PubMed  Google Scholar 

  58. Lange-Sperandio B, Cachat F, Thornhill BA, Chevalier RL (2002) Selectins mediate macrophage infiltration in obstructive nephropathy in newborn mice. Kidney Int 61:516–524

    CAS  PubMed  Google Scholar 

  59. Lange-Sperandio B, Fulda S, Vandewalle A, Chevalier RL (2003) Macrophages induce apoptosis in proximal tubule cells. Pediatr Nephrol 18:335–341

    PubMed  Google Scholar 

  60. Stephan M, Conrad S, Eggert T, Heuer R, Fernandez S, Huland H (2002) Urinary concentration and tissue messenger RNA expression of monocyte chemoattractant protein-1 as an indicator of the degree of hydronephrotic atrophy in partial ureteral obstruction. J Urol 167:1497–1502

    PubMed  Google Scholar 

  61. Fukuda K, Yoshitomi K, Yanagida T, Tokumoto M, Hirakata H (2001) Quantification of TGF-β1 mRNA along rat nephron in obstructive nephropathy. Am J Physiol 281:F513–F521

    CAS  Google Scholar 

  62. Johnson DW, Saunders HJ, Baxter RC, Feld MJ, Pollock CA (1998) Paracrine stimulation of human renal fibroblasts by proximal tubule cells. Kidney Int 54:747–757

    CAS  PubMed  Google Scholar 

  63. Seseke F, Thelen P, Ringert RH (2004) Characterization of an animal model of spontaneous congenital unilateral obstructive uropathy by cDNA microarray analysis. Eur Urol 45:374–381

    CAS  PubMed  Google Scholar 

  64. Liapis H, Doshi RH, Watson MA, Liapis A, Steinhardt GF (2002) Reduced renin expression and altered gene transcript profiles in multicystic dysplastic kidneys. J Urol 168:1816–1820

    CAS  PubMed  Google Scholar 

  65. Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG (2002) Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 110:341–350

    CAS  PubMed  Google Scholar 

  66. Butt MJ, Tarantal AF, Jimenez DF, Matsell DG (2007) Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction. Kidney Int 72:936–944

    CAS  PubMed  Google Scholar 

  67. Chung KH, Gomez RA, Chevalier RL (1995) Regulation of renal growth factors and clusterin by angiotensin AT1 receptors during neonatal ureteral obstruction. Am J Physiol 268:F1117–F1123

    CAS  PubMed  Google Scholar 

  68. Norwood VF, Carey RM, Geary KM, Jose PA, Gomez RA, Chevalier RL (1994) Neonatal ureteral obstruction stimulates recruitment of renin-secreting renal cortical cells. Kidney Int 45:1333–1339

    CAS  PubMed  Google Scholar 

  69. Kawada N, Moriyama T, Ando A, Fukunaga M, Miyata T, Kurokawa K, Imai E, Hori M (1999) Increased oxidative stress in mouse kidneys with unilateral ureteral obstruction. Kidney Int 56:1004–1013

    CAS  PubMed  Google Scholar 

  70. Pat B, Yang T, Kong C, Watters D, Johnson DW, Gobe G (2005) Activation of ERK in renal fibrosis after unilateral ureteral obstruction: modulation by antioxidants. Kidney Int 67:931–943

    CAS  PubMed  Google Scholar 

  71. Agarwal R (2002) Proinflammatory effects of oxidative stress in chronic kidney disease: role of additional angiotensin II blockade. Am J Physiol 284:F863–F869

    Google Scholar 

  72. Kinter M, Wolstenholme JT, Thornhill BA, Newton EA, McCormick ML, Chevalier RL (1999) Unilateral ureteral obstruction impairs renal antioxidant enzyme activation during sodium depletion. Kidney Int 55:1327–1334

    CAS  PubMed  Google Scholar 

  73. Ricardo SD, Ding G, Eufemio M, Diamond JR (1997) Antioxidant expression in experimental hydronephrosis: role of mechanical stretch and growth factors. Am J Physiol 272:F789–F798

    CAS  PubMed  Google Scholar 

  74. Chevalier RL, Peach MJ (1985) Hemodynamic effects of enalapril on neonatal chronic partial ureteral obstruction. Kidney Int 28:891–898

    CAS  PubMed  Google Scholar 

  75. Beharrie A, Franc-Guimond J, Rodriguez MM, Au J, Zilleruelo G, Abitbol CL (2004) A functional immature model of chronic partial ureteral obstruction. Kidney Int 65:1155–1161

    PubMed  Google Scholar 

  76. McDougal WS (1982) Pharmacologic preservation of renal mass and function in obstructive uropathy. J Urol 128:418–421

    CAS  PubMed  Google Scholar 

  77. Chen CO, Park MH, Forbes MS, Thornhill BA, Kiley SC, Yoo KH, Chevalier RL (2007) Angiotensin converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat. Am J Physiol Renal Physiol 292:F946–F955

    CAS  PubMed  Google Scholar 

  78. Coleman CM, Minor JJ, Burt LE, Thornhill BA, Forbes MS, Chevalier RL (2007) Angiotensin AT1 receptor inhibition exacerbates renal injury resulting from partial unilateral ureteral obstruction in the neonatal rat. Am J Physiol 293:F262–F268

    Article  CAS  Google Scholar 

  79. Hanss BG, Lewy JE, Vari RC (1994) Alterations in glomerular dynamics in congenital, unilateral hydronephrosis. Kidney Int 46:48–57

    CAS  PubMed  Google Scholar 

  80. Yanagisawa H, Morrissey J, Morrison AR, Purkerson ML, Klahr S (1990) Role of ANG II in eicosanoid production by isolated glomeruli from rats with bilateral ureteral obstruction. Am J Physiol 258:F85–F93

    CAS  PubMed  Google Scholar 

  81. Hammad FT, Wheatley AM, Davis G (2000) Long-term renal effects of unilateral ureteral obstruction and the role of endothelin. Kidney Int 58:242–250

    CAS  PubMed  Google Scholar 

  82. Reyes AA, Martin D, Settle S, Klahr S (1992) EDRF role in renal function and blood pressure of normal rats and rats with obstructive uropathy. Kidney Int 41:403–413

    CAS  PubMed  Google Scholar 

  83. Foxall PJD, Bewley S, Neild GH, Rodeck CH, Nicholson JK (1995) Analysis of fetal and neonatal urine using proton nuclear magnetic resonance spectroscopy. Arch Dis Child Fetal Neonatal 73:F153–F157

    CAS  Google Scholar 

  84. Murer L, Addabbo F, Carmosino M, Procino G, Tamma G, Montini G, Rigamonti W, Zucchetta P, della Vella M, Venturini A, Zacchello G, Svelto M, Valenti G (2004) Selective decrease in urinary aquaporin 2 and increase in prostaglandin E2 excretion is associated with postobstructive polyuria in human congenital hydronephrosis. J Am Soc Nephrol 15:2705–2712

    CAS  PubMed  Google Scholar 

  85. Claesson G, Svensson L, Robertson B, Josephson S, Cederlund T (1989) Experimental obstructive hydronephrosis in newborn rats. XI. A one-year follow-up study of renal function and morphology. J Urol 142:1602–1607

    CAS  PubMed  Google Scholar 

  86. Li C, Wang W, Kwon TH, Isikay L, Wen JG, Marples D, Djurhuus JC, Stockwell A, Knepper MA, Nielsen S, Frokiaer J (2001) Downregulation of AQP1, -2, and -3 after ureteral obstruction is associated with a long-term urine-concentrating defect. Am J Physiol 281:F163–F171

    CAS  Google Scholar 

  87. Boubaker A, Prior JO, Meyrat B, Delaloye AB (2003) Unilateral ureteropelvic junction obstruction in children: long-term followup after unilateral pyeloplasty. J Urol 170:575–579

    PubMed  Google Scholar 

  88. Chertin B, Pollack A, Koulikov D, Rabinowitz R, Hain D, Hadas-Halperin I, Farkas A (2006) Conservative treatment of ureteropelvic junction obstruction in children with antenatal diagnosis of hydronephrosis: lessons learned after 16 years of follow-up. Eur Urol 49:734–739

    PubMed  Google Scholar 

  89. Eskild-Jensen A, Jorgensen TM, Olsen LH, Djurhuus JC, Frokiær J (2003) Renal function may not be restored when using decreasing differential function as the criterion for surgery in unilateral hydronephrosis. BJU Int 92:779–782

    CAS  PubMed  Google Scholar 

  90. Chiou YY, Chiu NT, Wang ST, Cheng HL, Tang MJ (2004) Factors associated with the outcomes of children with unilateral ureteropelvic junction obstruction. J Urol 171:397–402

    PubMed  Google Scholar 

  91. Shi Y, Pedersen M, Li C, Wen JG, Thomsen K, Stodkilde-Jorgensen H, Jorgensen TM, Knepper MA, Nielsen S, Djurhuus JC, Frokiaer J (2004) Early release of neonatal ureteral obstruction preserves renal function. Am J Physiol 286:F1087–F1099

    CAS  Google Scholar 

  92. Chevalier RL, Thornhill BA, Chang AY (2000) Unilateral ureteral obstruction in neonatal rats leads to renal insufficiency in adulthood. Kidney Int 58:1987–1995

    CAS  PubMed  Google Scholar 

  93. Fenghua W, Junjie S, Gaoyan D, Jiacong M (2009) Does intervention in utero preserve the obstructed kidneys of fetal lambs? A histological, cytological, and molecular study. Pediatr Res 66:145–148

    PubMed  Google Scholar 

  94. Hughson MD, Farris AB, Douglas-Denton R, Hoy WE, Bertram JF (2003) Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int 63:2113–2122

    PubMed  Google Scholar 

  95. Hoy WE, Rees M, Kile E, Mathews JD, Wang Z (1999) A new dimension to the Barker hypothesis: low birthweight and susceptibility to renal disease. Kidney Int 56:1072–1077

    CAS  PubMed  Google Scholar 

  96. Luyckx VA, Brenner BM (2005) Low birth weight, nephron number, and kidney disease. Kidney Int 68:S68–S77

    Google Scholar 

  97. Elder JS, Stansbrey R, Dahms BB, Selzman AA (1995) Renal histological changes secondary to ureteropelvic junction obstruction. J Urol 154:719–722

    CAS  PubMed  Google Scholar 

  98. Stock JA, Krous HF, Heffernan J, Packer M, Kaplan GW (1995) Correlation of renal biopsy and radionuclide renal scan differential function in patients with unilateral ureteropelvic junction obstruction. J Urol 154:716–718

    CAS  PubMed  Google Scholar 

  99. Pascual L, Oliva J, Vega J, Principi I, Valles P (1998) Renal histology in ureteropelvic junction obstruction: are histological changes a consequence of hyperfiltration? J Urol 160:976–979

    CAS  PubMed  Google Scholar 

  100. Zhang PL, Peters CA, Rosen S (2000) Ureteropelvic junction obstruction: morphological and clinical studies. Pediatr Nephrol 14:820–826

    CAS  PubMed  Google Scholar 

  101. Roth KS, Carter WH Jr, Chan JCM (2001) Obstructive nephropathy in children: long-term progression after relief of posterior urethral valve. Pediatrics 107:1004–1010

    CAS  PubMed  Google Scholar 

  102. Biard JM, Johnson MP, Carr MC, Wilson RD, Hedrick HL, Pavlock C, Adzick NS (2005) Long-term outcomes in children treated by prenatal vesicoamniotic shunting for lower urinary tract obstruction. Obstet Gynecol 106:503–508

    PubMed  Google Scholar 

  103. Edouga D, Hugueny B, Gasser B, Bussières L, Laborde K (2001) Recovery after relief of fetal urinary obstruction: morphological, functional and molecular aspects. Am J Physiol 281:F26–F37

    CAS  Google Scholar 

  104. Hoy WE, Hughson MD, Bertram JF, Douglas-Denton R, Amann K (2005) Nephron number, hypertension, renal disease, and renal failure. J Am Soc Nephrol 16:2557–2564

    PubMed  Google Scholar 

  105. Peters CA (1995) Urinary tract obstruction in children. J Urol 154:1874–1883

    CAS  PubMed  Google Scholar 

  106. Biomarkers Definitions Working Group (2001) Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95

    Google Scholar 

  107. Decramer S, Wittke S, Mischak H, Zurbig P, Walden M, Bouissou F, Bascands JL, Schanstra JP (2006) Predicting the clinical outcome of congenital unilateral ureteropelvic junction obstruction in newborn by urinary proteome analysis. Nat Med 12:398–400

    CAS  PubMed  Google Scholar 

  108. Zurbig P, Decramer S, Dakna M, Jantos J, Good DM, Coon JJ, Bandin F, Mischak H, Bascands JL, Schanstra JP (2009) The human urinary proteome reveals high similarity between kidney aging and chronic kidney disease. Proteomics 9:2108–2117

    PubMed  Google Scholar 

  109. Lee RS, Monigatti FM, Lutchman M, Patterson T, Budnik B, Steen JAJ, Freeman MR, Steen H (2008) Temporal variations of the postnatal rat urinary proteome as a reflection of systemic maturation. Proteomics 8:1097–1112

    CAS  PubMed  Google Scholar 

  110. Furness PD III, Maizels M, Han SW, Cohn RA, Cheng EY (1999) Elevated bladder urine concentration of transforming growth factor-β1 correlates with upper urinary tract obstruction in children. J Urol 162:1033–1036

    PubMed  Google Scholar 

  111. Yang SP, Woolf AS, Yuan HT, Scott RJ, Risdon RA, O'Hare MJ, Winyard PJD (2000) Potential biological role of transforming growth factor-β1 in human congenital kidney malformations. Am J Pathol 157:1633–1647

    CAS  PubMed  Google Scholar 

  112. Grandaliano G, Gesualdo L, Bartoli F, Ranieri E, Monno R, Leggio A, Paradies G, Caldarulo E, Infante B, Schena FP (2000) MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy. Kidney Int 58:182–192

    CAS  PubMed  Google Scholar 

  113. Eardley KS, Zehnder D, Quinkler M, Lepenies J, Bates RL, Savage CO, Howie AJ, Adu D, Cockwell P (2006) The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease. Kidney Int 69:1189–1197

    CAS  PubMed  Google Scholar 

  114. Guron G, Friberg P (2000) An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertens 18:123–137

    CAS  PubMed  Google Scholar 

  115. Kagami S, Border WA, Miller DE, Noble NA (1994) Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-Beta expression in rat glomerular mesangial cells. J Clin Invest 93:2431–2437

    CAS  PubMed  Google Scholar 

  116. Ardissino G, Vigano S, Testa S, Dacco V, Paglialonga F, Leoni A, Belingheri M, Avolio L, Ciofani A, Claris-Appiani A, Cusi D, Edefonti A, Ammenti A, Cecconi M, Fede C, Ghio L, La Manna A, Maringhini S, Papalia T, Pela I, Pisanello L, Ratsch IM (2007) 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 22:2525–2530

    PubMed  Google Scholar 

  117. Chevalier RL, Goyal S, Thornhill BA (1999) EGF improves recovery following relief of unilateral ureteral obstruction in the neonatal rat. J Urol 162:1532–1536

    CAS  PubMed  Google Scholar 

  118. Chevalier RL, Goyal S, Kim A, Chang AY, Landau D, LeRoith D (2000) Renal tubulointerstitial injury from ureteral obstruction in the neonatal rat is attenuated by IGF-1. Kidney Int 57:882–890

    CAS  PubMed  Google Scholar 

  119. Fogo AB (2003) The potential for regression of renal scarring. Curr Opin Nephrol Hypertens 12:223–225

    PubMed  Google Scholar 

  120. Eddy AA (2005) Can renal fibrosis be reversed? Pediatr Nephrol 20:1369–1375

    PubMed  Google Scholar 

  121. Yoo KH, Thornhill BA, Forbes MS, Coleman CM, Marcinko ES, Liaw L, Chevalier RL (2006) Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. Kidney Int 70:1735–1741

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Virginia, Charlottesville, VA, USA

    Robert L. Chevalier, Barbara A. Thornhill, Michael S. Forbes & Susan C. Kiley

  2. Department of Pediatrics, University of Virginia Health System, Box 800386, Charlottesville, VA, 22908, USA

    Robert L. Chevalier

Authors
  1. Robert L. Chevalier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barbara A. Thornhill
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michael S. Forbes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Susan C. Kiley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert L. Chevalier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chevalier, R.L., Thornhill, B.A., Forbes, M.S. et al. Mechanisms of renal injury and progression of renal disease in congenital obstructive nephropathy. Pediatr Nephrol 25, 687–697 (2010). https://doi.org/10.1007/s00467-009-1316-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-009-1316-5

Keywords

Search

Navigation