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Chapter 14.1 - Fetal urinary tract obstruction

Pathophysiology

from Section 2 - Fetal disease

Published online by Cambridge University Press:  05 February 2013

By
Robert L. Chevalier
Edited by
Mark D. Kilby ,
Anthony Johnson  and
Dick Oepkes
Mark D. Kilby
Affiliation:
Department of Fetal Medicine, University of Birmingham
Anthony Johnson
Affiliation:
Baylor College of Medicine, Texas
Dick Oepkes
Affiliation:
Department of Obstetrics, Leiden University Medical Center
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Summary

Introduction

Fetal urinary tract obstruction accounts for the largest identifiable cause of kidney failure in infants and children. As for other congenital malformations, the etiology of most cases of congenital obstructive nephropathy is unknown. The site of obstruction along the urinary tract varies from the ureteropelvic junction (UPJ), to the ureterovesical junction and urethra. The hallmark of obstructive nephropathy is hydronephrosis with calyceal dilatation and renal parenchymal thinning depending on the location, timing, and severity of obstruction.

The human metanephros forms by the 5th week of gestation, and nephrogenesis continues through the 34th week, with ongoing perinatal and postnatal maturation through the first two years of life. Congenital obstructive lesions may be associated with abnormal renal development, resulting in renal agenesis, hypoplasia, or dysplasia. There are now substantial experimental data to support a direct effect of urinary tract obstruction on renal growth and development. The molecular basis of these effects has been investigated, suggesting a role for central regulators of epithelial differentiation, such as Wilms tumor-1 (WT1) and paired box gene 2 (PAX2), regulators of stromal development and extracellular matrix formation, as well as mediators of cell growth and survival, such as angiotensin, transforming growth factor-β (TGFβ), and B-cell lymphoma-2 (Bcl-2) [1].

Keywords

renal functional responsekidney failurenephronobstructive uropathyfetal urinary tract obstructionangiotensin II inhibitorabnormal renal development
Type
Chapter
Information
Fetal Therapy
Scientific Basis and Critical Appraisal of Clinical Benefits
 , pp. 238 - 245
Publisher: Cambridge University Press
Print publication year: 2012

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References

Liapis, H. Biology of congenital obstructive nephropathy. Exp Nephrol 2003;93:87–91.Google Scholar
Peters, CA. Obstruction of the fetal urinary tract. J Am Soc Nephrol 1997;8:653–63.Google Scholar
Peters, CA. Animal models of fetal renal disease. Prenat Diagn 2001;21:917–23.Google Scholar
Matsell, DG, Tarantal, AF. Experimental models of fetal obstructive nephropathy. Pediatr Nephrol 2002;17:470–6.Google Scholar
Eskild-Jensen, A, Frokiaer, J, Djurhuus, JC, et al. Reduced number of glomeruli in kidneys with neonatally induced partial ureteropelvic obstruction in pigs. J Urol 2002;167:1435–9.Google Scholar
Liapis, H, Barent, B, Steinhardt, GF. Extracellular matrix in fetal kidney after experimental obstruction. J Urol 2001;166:1433–8.Google Scholar
Huang, WY, Peters, CA, Zurakowski, D, et al. Renal biopsy in congenital ureteropelvic junction obstruction: evidence for parenchymal maldevelopment. Kidney Int 2006;69:137–43.Google Scholar
Murer, L, Benetti, E, Centi, S, et al. Clinical and molecular markers of chronic interstitial nephropathy in congenital unilateral ureteropelvic junction obstruction. J Urol 2006;176:2668–73.Google Scholar
Shibata, S, Shigeta, M, Shu, Y, et al. Initial pathological events in renal dysplasia with urinary tract obstruction in utero. Virchows Arch Int J Pathol 2001;439:560–70.Google Scholar
Tarantal, AF, Han, VKM, Cochrum, KC, et al. Fetal rhesus monkey model of obstructive renal dysplasia. Kidney Int 2001;59:446–56.Google Scholar
Matsell, DG, Mok, A, Tarantal, AF. Altered primate glomerular development due to in utero urinary tract obstruction. Kidney Int 2002;61:1263–9.Google Scholar
Butt, MJ, Tarantal, AF, Jimenez, DF, et al. Collecting duct epithelial-mesenchymal transition in fetal urinary tract obstruction. Kidney Int 2007;72:936–44.Google Scholar
Mure, PY, Gelas, T, Benchaib, M, et al.: Complete unilateral ureteral obstruction in the fetal lamb. Part I: long-term outcomes of renal hemodynamics and anatomy. J Urol 2006;175:1541–7.Google Scholar
Ward, RM, Starr, NT, Snow, BW, et al. Serial renal function in an ovine model of unilateral fetal urinary tract obstruction. J Urol 1989;142:652–6.Google Scholar
Glick, PL, Harrison, MR, Adzick, NS et al. Correction of congenital hydronephrosis in utero IV: in utero decompression prevents renal dysplasia. J Ped Surg 1984;19:649–57.Google Scholar
Mure, PY, Gelas, T, Dijoud, F, et al. Complete unilateral ureteral obstruction in the fetal lamb. Part II: Long-term outcomes of renal tissue development. J Urol 2006;175:1548–58.Google Scholar
Fenghua, W, Junjie, S, Gaoyan, D, et al. Does intervention in utero preserve the obstructed kidneys of fetal lambs? A histological, cytological, and molecular study. Pediatr Res 2009;66:145–8.Google Scholar
Kitagawa, H, Pringle, KC, Zuccollo, J, et al. Glomerular size in renal dysplasia secondary to obstructive uropathy: a further exploration of the fetal lamb model. J Pediatr Surg 2000;35:1651–5.Google Scholar
Steinhardt, GF, Salinas-Madrigal, L, DeMello, D, et al. Experimental ureteral obstruction in the fetal opossum: histological assessment. J Urol 1994;152:2133–8.Google Scholar
McVary, KT, Maizels, M. Urinary obstruction reduces glomerulogenesis in the developing kidney: a model in the rabbit. J Urol 1989;142:646–51.Google Scholar
Fetterman, GH, Ravitch, MM, Sherman, FE. Cystic changes in fetal kidneys following ureteral ligation: studies by microdissection. Kidney Int 1974;5:111–21.Google Scholar
Airik, R, Kispert, A. Down the tube of obstructive nephropathies: the importance of tissue interactions during ureter development. Kidney Int 2007;72:1459–67.Google Scholar
Yokoyama, H, Wada, T, Kobayashi, K, et al. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-1 null mutant mice develop renal lesions mimicking obstructive nephropathy. Nephrol Dial Transpl 2002;17 Suppl 9:39 Google Scholar
Miyazaki, Y, Tsuchida, S, Nishimura, H, et al. Angiotensin induces the urinary peristaltic machinery during the perinatal period. J Clin Invest 1998;102:1489–97.Google Scholar
Yoo, KH, Thornhill, BA, Forbes, MS, et al. Inducible nitric oxide synthase modulates hydronephrosis following partial or complete unilateral ureteral obstruction in the neonatal mouse. Am J Physiol 2010;298:F62–F71.Google Scholar
Chang, CP, McDill, BW, Neilson, JR, et al. Calcineurin is required in urinary tract mesenchyme for the development of the pyeloureteral peristaltic machinery. J Clin Invest 2004;113:1051–8.Google Scholar
Mendelsohn, C. Functional obstruction: the renal pelvis rules. J Clin Invest 2004;113:957–9.Google Scholar
Lye, CM, Fasano, L, Woolf, AS. Ureter myogenesis: putting Teashirt into context. J Am Soc Nephrol 2010;21:24–30.Google Scholar
Hurtado, R, Bub, G, Herzlinger, D. The pelvis-kidney junction contains HCN3, a hyperpolarization-activated cation channel that triggers ureter peristalsis. Kidney Int 2010;77:500–8.Google Scholar
Solari, V, Piotrowska, AP, Puri, P. Altered expression of interstitial cells of Cajal in congenital ureteropelvic junction obstruction. J Urol 2003;170:2420–2.Google Scholar
Kajbafzadeh, AM, Payabvash, S, Salmasi, AH, et al. Smooth muscle cell apoptosis and defective neural development in congenital ureteropelvic junction obstruction. J Urol 2006;176:718–23.Google Scholar
Gasser, B, Mauss, Y, Ghnassia, JP et al. 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 1993;8:371–84.Google Scholar
Poucell-Hatton, S, Huang, M, Bannykh, S, et al. Fetal obstructive uropathy: patterns of renal pathology. Pediatr Devel Pathol 2000;3:223–31.Google Scholar
Daiekha-Dahmane, F, Dommergues, M, Muller, F, et al. Development of human fetal kidney in obstructive uropathy: correlations with ultrasonography and urine biochemistry. Kidney Int 1997;52:21–32.Google Scholar
Hiatt, MJ, Ivanova, L, Toran, N, et al. Remodeling of the fetal collecting duct epithelium. Am J Pathol 2010;176:630–7.Google Scholar
Harrison, MR, Ross, N, Noall, R, et al. Correction of congenital hydronephrosis in utero I. The model: fetal urethral obstruction produces hydronephrosis and pulmonary hypoplasia in fetal lambs. J Pediatr Surg 1983;18:247–56.Google Scholar
Harrison, MR, Nakayama, DK, Noall, R, et al. Correction of congenital hydronephrosis in utero II. Decompression reverses the effects of obstruction on the fetal lung and urinary tract. J Pediatr Surg 1982;17:965–74.Google Scholar
Pringle, KC, Zuccollo, J, Kitagawa, H, et al. Renal dysplasia produced by obstructive uropathy in the fetal lamb. Pathology 2003;35:518–21.Google Scholar
Edouga, D, Hugueny, B, Gasser, B, et al. Recovery after relief of fetal urinary obstruction: morphological, functional and molecular aspects. Am J Physiol 2001;281:F26–F37.Google Scholar
Gotoh, H, Masuzaki, H, Taguri, H, et al. Effect of experimentally induced urethral obstruction and surgical decompression in utero on renal development and function in rabbits. Early Hum Dev 1998;52:111–23.Google Scholar
Singh, S, Robinson, M, Nahi, F, et al. Identification of a unique transgenic mouse line that develops megabladder, obstructive uropathy, and renal dysfunction. J Am Soc Nephol 2007;18:461–71.Google Scholar
Hughson, MD, Farris, AB, Douglas-Denton, R, et al. Glomerular number and size in autopsy kidneys: the relationship to birth weight. Kidney Int 2003;63:2113–22.Google Scholar
Gluckman, PD, Hanson, MA, Cooper, C, et al. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 2008;359:61–73.Google Scholar
Hedrick, HL, Flake, AW, Crombleholme, TM, et al. History of fetal diagnosis and therapy: Children’s Hospital of Philadelphia experience. Fetal Diagn Ther 2003;18:65–82.Google Scholar
Rodriguez, MM, Gomez, A, Abitbol, C et al. Comparative renal histomorphometry: a case study of oligonephropathy of prematurity. Pediatr Nephrol 2005;20:945–9.Google Scholar
Thornhill, BA, Burt, LA, Chen, C, et al. Variable chronic partial ureteral obstruction in the neonatal rat: a new model of ureteropelvic junction obstruction. Kidney Int 2005;67:42–52.Google Scholar
Chevalier, RL, Thornhill, BA, Chang, AY, et al. Recovery from release of ureteral obstruction in the rat: relationship to nephrogenesis. Kidney Int 2002;61:2033–43.Google Scholar
Cachat, F, Lange-Sperandio, B, Chang, AY, et al. Ureteral obstruction in neonatal mice elicits segment-specific tubular cell responses leading to nephron loss. Kidney Int 2003;63:564–75.Google Scholar
Chevalier, RL, Chung, KH, Smith, CD, et al. Renal apoptosis and clusterin following ureteral obstruction: the role of maturation. J Urol 1996;156:1474–9.Google Scholar
Thornhill, BA, Forbes, MS, Marcinko, ES, et al. Glomerulotubular disconnection in neonatal mice after relief of partial ureteral obstruction. Kidney Int 2007;72:1103–12.Google Scholar
Forbes, MS, Thornhill, BA, Chevalier, RL. Proximal tubular injury and rapid formation of atubular glomeruli in mice with unilateral ureteral obstruction: a new look at an old model. Am J Physiol 2011;301:F110–17.Google Scholar
Chevalier, RL, Forbes, MS. Generation and evolution of atubular glomeruli in the progression of renal disorders. J Am Soc Nephrol 2008;19:197–206.Google Scholar
Chevalier, RL, Thornhill, BA, Forbes, MS, et al. Mechanisms of renal injury and progression of renal disease in congenital obstructive nephropathy. Pediatr Nephrol 2010;25:687–97.Google Scholar
Chevalier, RL. Obstructive nephropathy: towards biomarker discovery and gene therapy. Nat Clin Prac Nephrol 2006;2:157–68.Google Scholar
Chevalier, RL, Kim, A, Thornhill, BA, et al. Recovery following relief of unilateral ureteral obstruction in the neonatal rat. Kidney Int 1999;55:793–807.Google Scholar
Valles, P, Pascual, L, Manucha, W, et al. Role of endogenous nitric oxide in unilateral ureteropelvic junction obstruction in children. Kidney Int 2003;63:1104–15.Google Scholar
Yoo, KH, Thornhill, BA, Forbes, MS, et al. Osteopontin regulates renal apoptosis and interstitial fibrosis in neonatal chronic unilateral ureteral obstruction. Kidney Int 2006;70:1735–41.Google Scholar
Fujinaka, H, Miyazaki, Y, Matsusaka, T, et al. Salutary role for angiotensin in partial urinary tract obstruction. Kidney Int 2000;58:2018–27.Google Scholar
Perico, N, Codreanu, I, Scheippati, A, et al. The future of renoprotection. Kidney Int 2005;68 (Suppl 97):S95–101.Google Scholar
Fern, RJ, Yesko, CM, Thornhill, BA, et al. Reduced angiotensinogen expression attenuates renal interstitial fibrosis in obstructive nephropathy in mice. J Clin Invest 1999;103:39–46.Google Scholar
Klahr, S, Ishidoya, S, Morrissey, J. Role of angiotensin II in the tubulointerstitial fibrosis of obstructive nephropathy. Am J Kidney Dis 1995;26:141–6.Google Scholar
Beharrie, A, Franc-Guimond, J, Rodriguez, MM, et al. A functional immature model of chronic partial ureteral obstruction. Kidney Int 2004;65:1155–61.Google Scholar
Pryde, PG, Sedman, AB, Nugent, CE, et al. Angiotensin-converting enzyme inhibitor fetopathy. J Am Soc Nephrol 1993;3:1575–82.Google Scholar
Chen, CO, Park, MH, Forbes, MS, et al. Angiotensin converting enzyme inhibition aggravates renal interstitial injury resulting from partial unilateral ureteral obstruction in the neonatal rat. Am J Physiol Renal Physiol 2007;292:F946–55.Google Scholar
Coleman, CM, Minor, JJ, Burt, LE, et al. Angiotensin AT1 receptor inhibition exacerbates renal injury resulting from partial unilateral ureteral obstruction in the neonatal rat. Am J Physiol 2007;293:F262–68.Google Scholar
Mitra, SC. Effect of cocaine on fetal kidney and bladder function. J Matern Fetal Med 1999;8:262–9.Google Scholar
Brace, RA, Wolf, EJ. Normal amniotic fluid volume changes throughout pregnancy. Am J Obstet Gynecol 1989;161:382–8.Google Scholar
Morris, RK, Malin, GL, Khan, KS, et al. Antenatal ultrasound to predict postnatal renal function in congenital lower urinary tract obstruction: systematic review of test accuracy. BJOG 2009;116:1290–9.Google Scholar
Dommergues, M, Muller, F, Ngo, S, et al. Fetal serum β2-microglobulin predicts postnatal renal function in bilateral uropathies. Kidney Int 2000;58:312–16.Google Scholar
Muller, F, Bernard, MA, Benkirane, A, et al. Fetal urine cystatin C as a predictor of postnatal renal function in bilateral uropathies. Clin Chem 1999;45:2292–3.Google Scholar
Nicolini, U, Spelzini, F. Invasive assessment of fetal renal abnormalities: urinalysis, fetal blood sampling and biopsy. Prenat Diagn 2001;21:964–9.Google Scholar
Morris, RK, Quinlan-Jones, E, Kilby, MD, et al. Systematic review of accuracy of fetal urine analysis to predict poor postnatal renal function in cases of congenital urinary tract obstruction. Prenat Diagn 2007;27:900–11.Google Scholar
Foxall, PJD, Bewley, S, Neild, GH, et al. Analysis of fetal and neonatal urine using proton nuclear magnetic resonance spectroscopy. Arch Dis Child Fetal Neonatal 1995;73:F153–57.Google Scholar
Murer, L, Addabbo, F, Carmosino, M, et al. 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 2004;15:2705–12.Google Scholar
Mandell, J, Peters, CA, Estroff, JA, et al. Human fetal compensatory renal growth. J Urol 1993;150:790–2.Google Scholar
Peters, CA, Gaertner, RC, Carr, MC, et al. Fetal compensatory renal growth due to unilateral ureteral obstruction. J Urol 1993;150:597–600.Google Scholar
Yoo, KH, Thornhill, BA, Forbes, MS, et al. Compensatory renal growth due to neonatal ureteral obstruction: implications for clinical studies. Pediatr Nephrol 2006;21:368–75.Google Scholar

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