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Umbilical artery histomorphometry: a link between the intrauterine environment and kidney development

Published online by Cambridge University Press:  06 March 2017

M. J. DeFreitas ,
D. Mathur ,
W. Seeherunvong ,
T. Cano ,
C. P. Katsoufis ,
S. Duara ,
S. Yasin ,
G. Zilleruelo ,
M. M. Rodriguez  and
C. L. Abitbol
M. J. DeFreitas*
Affiliation:
Pediatric Nephrology, School of Medicine, University of Miami, Miami, FL, USA
D. Mathur
Affiliation:
Pediatric Pathology, University of Miami, Miami, FL, USA
W. Seeherunvong
Affiliation:
Pediatric Nephrology, School of Medicine, University of Miami, Miami, FL, USA
T. Cano
Affiliation:
Pediatric Nephrology, School of Medicine, University of Miami, Miami, FL, USA
C. P. Katsoufis
Affiliation:
Pediatric Nephrology, School of Medicine, University of Miami, Miami, FL, USA
S. Duara
Affiliation:
Neonatology, University of Miami, Miami, FL, USA
S. Yasin
Affiliation:
Obstetrics/Gynecology, University of Miami, Miami, FL, USA
G. Zilleruelo
Affiliation:
Pediatric Nephrology, School of Medicine, University of Miami, Miami, FL, USA
M. M. Rodriguez
Affiliation:
Pediatric Pathology, University of Miami, Miami, FL, USA
C. L. Abitbol
Affiliation:
Pediatric Nephrology, School of Medicine, University of Miami, Miami, FL, USA
*
*Address for correspondence: M. J. DeFreitas, Pediatric Nephrology, School of Medicine, University of Miami, 1611 NW 12th Ave, Institute Annex, Suite 504, Miami, FL 33136-1015, USA. (Email [email protected])
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Abstract

Prematurity is a risk factor for hypertension, vascular stiffness, nephron deficit and adult onset cardiorenal disease. The vascular tree and kidneys share morphogenic drivers that promote maturation in utero before 36 weeks of gestation. Vascular elastin accrual terminates after birth leaving collagen to promote vascular stiffness. Our objective was to determine if the histomorphometry of the umbilical artery, an extension of the aorta, parallels nephron mass across gestational age groups. From a cohort of 54 newborns, 32 umbilical cord specimens were adequate for evaluation. The umbilical cord was sectioned, stained with trichrome, and digitalized. Muscular and collagenous areas of the umbilical artery were measured in pixels using the Image J 1.48q software. Total kidney volume was measured by ultrasound and factored by body surface area (TKV/BSA). The umbilical artery total area was significantly greater in term v. preterm infants (9.3±1.3 v. 7.0±2.0 mm2; P<0.05) and increased with gestational age; while the percent muscular and collagen areas were independent of gestational age (R2=0.04; P=ns). Percent muscular area correlated positively with TKV/BSA (r=0.53; P=0.002); while an increase in collagen correlated inversely with kidney mass (r=−0.53; P=0.002). In conclusion, an enhanced % muscular area and presumed vascular elasticity was associated with increased renal mass in all infants. Umbilical artery histomorphometry provides a link between the intrauterine environment, vascular and kidney development.

Keywords

cardiorenal diseasekidney developmentprematurityvascular development
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 3 , June 2017 , pp. 349 - 356
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2017 

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References

1. Barker, DJ, Thornburg, KL. Placental programming of chronic diseases, cancer and lifespan: a review. Placenta. 2013; 34, 841–845.Google Scholar
2. Luyckx, VA, Bertram, JF, Brenner, BM, et al. Effect of fetal and child health on kidney development and long-term risk of hypertension and kidney disease. Lancet. 2013; 382, 273–283.Google Scholar
3. Kelishadi, R, Poursafa, P. A review on the genetic, environmental, and lifestyle aspects of the early-life origins of cardiovascular disease. Curr Probl Pediatr Adolesc Health Care. 2014; 44, 54–72.CrossRefGoogle ScholarPubMed
4. Mu, M, Wang, SF, Sheng, J, et al. Birth weight and subsequent blood pressure: a meta-analysis. Arch Cardiovasc Dis. 2012; 105, 99–113.Google Scholar
5. de Jong, F, Monuteaux, MC, van Elburg, RM, et al. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension. 2012; 59, 226–234.Google Scholar
6. Abitbol, CL, Seeherunvong, W, Galarza, MG, et al. Neonatal kidney size and function in preterm infants: what is a true estimate of glomerular filtration rate? J Pediatr. 2014; 164, 1026–1031.Google Scholar
7. Brenner, BM, Chertow, GM. Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury. Am J Kidney Dis. 1994; 23, 171–175.Google Scholar
8. Abitbol, CL, Ingelfinger, JR. Nephron mass and cardiovascular and renal disease risks. Semin Nephrol. 2009; 29, 445–454.Google Scholar
9. Hsu, CW, Yamamoto, KT, Henry, RK, et al. Prenatal risk factors for childhood CKD. J Am Soc Nephrol. 2014; 25, 2105–2111.Google Scholar
10. Luyckx, VA, Brenner, BM. The clinical importance of nephron mass. J Am Soc Nephrol. 2010; 21, 898–910.Google Scholar
11. Clough, GF, Norman, M. The microcirculation: a target for developmental priming. Microcirculation. 2011; 18, 286–297.Google Scholar
12. Tauzin, L, Rossi, P, Giusano, B, et al. Characteristics of arterial stiffness in very low birth weight premature infants. Pediatr Res. 2006; 60, 592–596.CrossRefGoogle ScholarPubMed
13. Martyn, CN, Greenwald, SE. Impaired synthesis of elastin in walls of aorta and large conduit arteries during early development as an initiating event in pathogenesis of systemic hypertension. Lancet. 1997; 350, 953–955.CrossRefGoogle Scholar
14. Blanco, MV, Vega, HR, Giuliano, R, et al. Histomorphometry of umbilical cord blood vessels in preeclampsia. J Clin Hypertens. 2011; 13, 30–34.Google Scholar
15. Togni, FA, Araujo Junior, E, Vasques, FA, et al. The cross-sectional area of umbilical cord components in normal pregnancy. Int J Gynaecol Obstet. 2007; 96, 156–161.Google Scholar
16. Raio, L, Ghezzi, F, Di Naro, E, et al. Umbilical cord morphologic characteristics and umbilical artery Doppler parameters in intrauterine growth-restricted fetuses. J Ultrasound Med. 2003; 22, 1341–1347.Google Scholar
17. Kitamoto, Y, Tokunaga, H, Miyamoto, K, et al. VEGF is an essential molecule for glomerular structuring. Nephrol Dial Transplant. 2002; 17(Suppl. 9), 25–27.Google Scholar
18. Del Porto, F, Mariotti, A, Ilardi, M, et al. Kidney vasculogenesis and angiogenesis: role of vascular endothelial growth factor. Eur Rev Med Pharmacol Sci. 1999; 3, 149–153.Google Scholar
19. Blanco, MV, Vega, HR, Guerri-Guttenberg, R, et al. Histopathology and histomorphometry of umbilical cord blood vessels: findings in normal and high risk pregnancies. Artery Res. 2011; 5, 50–57.Google Scholar
20. Junek, T, Baum, O, Läuter, H, et al. Pre-eclampsia associated alterations of the elastic fibre system in umbilical cord vessels. Anat Embryol. 2000; 201, 291–303.Google Scholar
21. Carmody, JB, Swanson, JR, Rhone, ET, et al. Recognition and reporting of AKI in very low birth weight infants. Clin J Am Soc Nephrol. 2014; 9, 2036–2043.Google Scholar
22. Schneider, CA, Rasband, WS, Eliceiri, KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012; 9, 671–675.Google Scholar
23. Hricak, H, Lieto, RP. Sonographic determination of renal volume. Radiology. 1983; 148, 311–312.Google Scholar
24. Du Bois, D, Du Bois, EF. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition. 1989; 5, 303–311.Google Scholar
25. Cohen, HL, Cooper, J, Eisenberg, P, et al. Normal length of fetal kidneys: sonographic study in 397 obstetric patients. Am J Roentgenol. 1991; 157, 545–548.Google Scholar
26. Rodriguez, MM, Gomez, AH, Abitbol, CL, et al. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants. Pediatr Dev Pathol. 2004; 7, 17–25.CrossRefGoogle ScholarPubMed
27. Sutherland, MR, Gubhaju, L, Moore, L, et al. Accelerated maturation and abnormal morphology in the preterm neonatal kidney. J Am Soc Nephrol. 2011; 22, 1365–1374.Google Scholar
28. Faa, G, Gerosa, C, Fanni, D, et al. Marked interindividual variability in renal maturation of preterm infants: lessons from autopsy. J Matern Fetal Neonatal Med. 2010; 23(Suppl. 3), 129–133.CrossRefGoogle ScholarPubMed
29. Crobe, A, Desogus, M, Sanna, A, et al. Decreasing podocyte number during human kidney intrauterine development. Am J Physiol Renal Physiol. 2014; 307, F1033–F1040.Google Scholar
30. Chaturvedi, S, Ng, KH, Mammen, C. The path to chronic kidney disease following acute kidney injury: a neonatal perspective. Pediatr Nephrol. 2017; 32, 227–241.Google Scholar
31. Weintraub, AS, Connors, J, Carey, A, et al. The spectrum of onset of acute kidney injury in premature infants less than 30 weeks gestation. J Perinatol. 2016; 36, 474–480.Google Scholar
32. Abitbol, CL, DeFreitas, MJ, Strauss, J. Assessment of kidney function in preterm infants: lifelong implications. Pediatr Nephrol. 2016; 31, 2213–2222.Google Scholar
33. Zhang, Z, Quinlan, J, Hoy, W, et al. A common RET variant is associated with reduced newborn kidney size and function. J Am Soc Nephrol. 2008; 19, 2027–2034.Google Scholar
34. Goodyer, P, Kurpad, A, Rekha, S, et al. Effects of maternal vitamin A status on kidney development: a pilot study. Pediatr Nephrol. 2007; 22, 209–214.Google Scholar
35. Hoy, WE, Hughson, MD, Singh, GR, et al. Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension. Kidney Int. 2006; 70, 104–110.Google Scholar
36. Fanni, D, Gerosa, C, Nemolato, S, et al. ‘Physiological’ renal regenerating medicine in VLBW preterm infants: could a dream come true? J Matern Fetal Neonatal Med. 2012; 25(Suppl. 3), 41–48.Google Scholar
37. Burkhardt, T, Matter, CM, Lohmann, C, et al. Decreased umbilical artery compliance and igf-I plasma levels in infants qwith intrauterine growth restriction – implications for fetal programming of hypertension. Placenta. 2009; 30, 136–141.Google Scholar
38. Lazdam, M, de la Horra, A, Pitcher, A, et al. Elevated blood pressure in offspring born premature to hypertensive pregnancy: is endothelial dysfunction the underlying vascular mechanism? Hypertension. 2010; 56, 159–165.CrossRefGoogle ScholarPubMed
39. Leeson, CP, Kattenhorn, M, Morley, R, et al. Impact of low birth weight and cardiovascular risk factors on endothelial function in early adult life. Circulation. 2001; 103, 1264–1268.Google Scholar
40. Cheung, YF, Wong, KY, Lam, BC, et al. Relation of arterial stiffness with gestational age and birth weight. Arch Dis Child. 2004; 89, 217–221.Google Scholar
41. Norman, M. Low birth weight and the developing vascular tree: a systematic review. Acta Paediatr. 2008; 97, 1165–1172.Google Scholar
42. Ligi, I, Simoncini, S, Tellier, E, et al. Altered angiogenesis in low birth weight individuals: a role for anti-angiogenic circulating factors. J Matern Fetal Neonatal Med. 2014; 27, 233–238.Google Scholar
43. Togni, FA, Araujo Junior, E, Moron, AF, et al. Reference intervals for the cross sectional area of the umbilical cord during gestation. J Perinat Med. 2007; 35, 130–134.Google Scholar
44. Di Naro, E, Ghezzi, F, Raio, L, et al. Umbilical cord morphology and pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2001; 96, 150–157.Google Scholar
45. Peyter, AC, Delhaes, F, Baud, D, et al. Intrauterine growth restriction is associated with structural alterations in human umbilical cord and decreased nitric oxide-induced relaxation of umbilical vein. Placenta. 2014; 35, 891–899.Google Scholar
46. Dodson, RB, Martin, JT, Hunter, KS, et al. Determination of hyperelastic properties for umbilical artery in preeclampsia from uniaxial extension tests. Eur J Obstet Gynecol Reprod Biol. 2013; 169, 207–212.Google Scholar
47. Davis, EF, Lazdam, M, Lewandowski, AJ, et al. Cardiovascular risk factors in children and young adults born to preeclamptic pregnancies: a systematic review. Pediatrics. 2012; 129, 1552–1561.Google Scholar
48. Kooijman, MN, Bakker, H, van der Heijden, AJ, et al. Childhood kidney outcomes in relation to fetal blood flow and kidney size. J Am Soc Nephrol. 2014; 25, 2616–2624.CrossRefGoogle ScholarPubMed
49. Verburg, BO, Geelhoed, JJ, Steegers, EA, et al. Fetal kidney volume and its association with growth and blood flow in fetal life: The Generation R Study. Kidney Int. 2007; 72, 754–761.Google Scholar
50. RG, IJ, Stehouwer, CD, Boomsma, DI. Evidence for genetic factors explaining the birth weight-blood pressure relation. Analysis in twins. Hypertension. 2000; 36, 1008–1012.Google Scholar
51. Ijzerman, RG, Boomsma, DI, Stehouwer, CD. Intrauterine environmental and genetic influences on the association between birthweight and cardiovascular risk factors: studies in twins as a means of testing the fetal origins hypothesis. Paediatr Perinat Epidemiol. 2005; 19(Suppl. 1), 10–14.CrossRefGoogle ScholarPubMed
52. Bergvall, N, Iliadou, A, Johansson, S, et al. Genetic and shared environmental factors do not confound the association between birth weight and hypertension: a study among Swedish twins. Circulation. 2007; 115, 2931–2938.CrossRefGoogle Scholar
53. Rajan, T, Barbour, SJ, White, CT, et al. Low birth weight and nephron mass and their role in the progression of chronic kidney disease: a case report on identical twins with Alport disease. Nephrol Dial Transplant. 2011; 26, 4136–4139.Google Scholar
54. Pottel, H. Measuring and estimating glomerular filtration rate in children. Pediatr Nephrol . 2017; 32, 249–263.Google Scholar
55. Abitbol, CL, Rodriguez, MM. The long-term renal and cardiovascular consequences of prematurity. Nat Rev Nephrol. 2012; 8, 265–274.Google Scholar
56. Carmody, JB, Charlton, JR. Short-term gestation, long-term risk: prematurity and chronic kidney disease. Pediatrics. 2013; 131, 1168–1179.Google Scholar