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Impact of prenatal and postnatal maternal environment on nephron endowment, renal function and blood pressure in the Lewis polycystic kidney rat

Published online by Cambridge University Press:  02 October 2018

A. Ding ,
S. L. Walton ,
K. M. Moritz  and
J. K. Phillips Open the ORCID record for J. K. Phillips [Opens in a new window]
A. Ding
Affiliation:
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
S. L. Walton
Affiliation:
School of Biomedical Sciences, University of Queensland, St Lucia, QLD, Australia
K. M. Moritz
Affiliation:
School of Biomedical Sciences, University of Queensland, St Lucia, QLD, Australia Child Health Research Centre, University of Queensland, St Lucia, QLD, Australia
J. K. Phillips*
Affiliation:
Department of Biomedical Science, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia
*
*Address for correspondence:J. K. Phillips, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia. E-mail: [email protected]
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Abstract

Maternal insufficiency during fetal development can have long-lasting effects on the offspring, most notably on nephron endowment. In polycystic kidney disease (PKD), variability in severity of disease is observed and maternal environment may be a modifying factor. In this study, we first established that in a rodent model of PKD, the Lewis polycystic kidney (LPK) rat’s nephron numbers are 25% lower compared with wildtype animals. We then investigated the effects of prenatal and postnatal maternal environment on phenotype and nephron number. LPK pups born from and raised by homozygous LPK dams (control) were compared with LPK pups cross-fostered onto heterozygous LPK dams to improve postnatal environment; with LPK pups born from and raised by heterozygous LPK dams to improve both prenatal and postnatal environment and with LPK pups born from and raised by Wistar Kyoto-LPK heterozygous dams to improve both prenatal and postnatal environment on a different genetic background. Improvement in both prenatal and postnatal environment improved postnatal growth, renal function and reduced blood pressure, most notably in animals with different genetic background. Animals with improved postnatal environment only showed improved growth and blood pressure, but to a lesser extent. All intervention groups showed increased nephron number compared with control LPK. In summary, prenatal and postnatal environment had significant effect in delaying progression and reducing severity of PKD, including nephron endowment.

Keywords

blood pressurebody weightmaternal environmentnephron endowmentpolycystic kidney disease
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Issue 2 , April 2019 , pp. 154 - 163
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018. 

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References

1. Barker, DJ. The origins of the developmental origins theory. J Intern Med. 2007; 261, 412–417.Google Scholar
2. Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359, 61–73.Google Scholar
3. Hoy, WE, Hughson, MD, Bertram, JF, Douglas-Denton, R, Amann, K. Nephron number, hypertension, renal disease, and renal failure. J Am Soc Nephrol. 2005; 16, 2557–2564.Google Scholar
4. Dorey, ES, Pantaleon, M, Weir, KA, Moritz, KM. Adverse prenatal environment and kidney development: implications for programming of adult disease. Reproduction. 2014; 147, R189–R198.Google Scholar
5. Hoy, WE, Hughson, MD, Zimanyi, M, et al. Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index. Clin Nephrol. 2010; 74(Suppl 1), S105–S112.Google Scholar
6. Bertram, JF, Cullen-McEwen, LA, Egan, GF, et al. Why and how we determine nephron number. Pediatr Nephrol. 2014; 29, 575–580.Google Scholar
7. Dickinson, H, Walker, DW, Cullen-McEwen, L, Wintour, EM, Moritz, K. The spiny mouse (Acomys cahirinus) completes nephrogenesis before birth. Am J Physiol Renal Physiol. 2005; 289, F273–F279.Google Scholar
8. Singh, RR, Denton, KM, Bertram, JF, Dowling, J, Moritz, KM. Urine-concentrating defects exacerbate with age in male offspring with a low-nephron endowment. Am J Physiol Renal Physiol. 2011; 301, F1168–F1176.Google Scholar
9. Singh, RR, Jefferies, AJ, Lankadeva, YR, et al. Increased cardiovascular and renal risk is associated with low nephron endowment in aged females: an ovine model of fetal unilateral nephrectomy. PLoS One. 2012; 7, e42400.Google Scholar
10. Wlodek, ME, Mibus, A, Tan, A, et al. Normal lactational environment restores nephron endowment and prevents hypertension after placental restriction in the rat. J Am Soc Nephrol. 2007; 18, 1688–1696.Google Scholar
11. Grantham, JJ. Clinical practice. Autosomal dominant polycystic kidney disease. N Engl J Med. 2008; 359, 1477–1485.Google Scholar
12. Chapman, AB, Devuyst, O, Eckardt, KU, et al. Autosomal-dominant polycystic kidney disease (ADPKD): executive summary from a kidney disease: improving global outcomes (KDIGO) controversies conference. Kidney Int. 2015; 88, 17–27.Google Scholar
13. Otto, EA, Trapp, ML, Schultheiss, UT, et al. NEK8 mutations affect ciliary and centrosomal localization and may cause nephronophthisis. J Am Soc Nephrol. 2008; 19, 587–592.Google Scholar
14. Perrichot, RA, Mercier, B, de Parscau, L, et al. Inheritance of a stable mutation in a family with early-onset disease. Nephron. 2001; 87, 340–345.Google Scholar
15. Devuyst, O, Persu, A, Vo-Cong, MT. Autosomal dominant polycystic kidney disease: modifier genes and endothelial dysfunction. Nephrol Dial Transplant. 2003; 18, 2211–2215.Google Scholar
16. Barker, DJ, Martyn, CN. The maternal and fetal origins of cardiovascular disease. J Epidemiol Community Health. 1992; 46, 8–11.Google Scholar
17. Dipple, KM, McCabe, ER. Modifier genes convert “simple” Mendelian disorders to complex traits. Mol Genet Metab. 2000; 71, 43–50.Google Scholar
18. Orskov, B, Christensen, KB, Feldt-Rasmussen, B, Strandgaard, S. Low birth weight is associated with earlier onset of end-stage renal disease in Danish patients with autosomal dominant polycystic kidney disease. Kidney Int. 2012; 81, 919–924.Google Scholar
19. McCooke, JK, Appels, R, Barrero, RA, et al. A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8. BMC Genomics. 2012; 13, 393.Google Scholar
20. Liu, S, Lu, W, Obara, T, et al. A defect in a novel Nek-family kinase causes cystic kidney disease in the mouse and in zebrafish. Development. 2002; 129, 5839–5846.Google Scholar
21. Phillips, JK, Hopwood, D, Loxley, RA, et al. Temporal relationship between renal cyst development, hypertension and cardiac hypertrophy in a new rat model of autosomal recessive polycystic kidney disease. Kidney Blood Press Res. 2007; 30, 129–144.Google Scholar
22. Consortium, S, Saar, K, Beck, A, et al. SNP and haplotype mapping for genetic analysis in the rat. Nat Genet. 2008; 40, 560–566.Google Scholar
23. Cullen-McEwen, LA, Armitage, JA, Nyengaard, JR, Moritz, KM, Bertram, JF. A design-based method for estimating glomerular number in the developing kidney. Am J Physiol Renal Physiol. 2011; 300, F1448–F1453.Google Scholar
24. Schindelin, J, Arganda-Carreras, I, Frise, E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9, 676–682.Google Scholar
25. Edmunds, JW, Jayapalan, S, DiMarco, NM, Saboorian, MH, Aukema, HM. Creatine supplementation increases renal disease progression in Han:SPRD-cy rats. Am J Kidney Dis. 2001; 37, 73–78.Google Scholar
26. Hales, CN, Ozanne, SE. For debate: fetal and early postnatal growth restriction lead to diabetes, the metabolic syndrome and renal failure. Diabetologia. 2003; 46, 1013–1019.Google Scholar
27. Eriksson, JG, Forsen, T, Tuomilehto, J, et al. Catch-up growth in childhood and death from coronary heart disease: longitudinal study. BMJ. 1999; 318, 427–431.Google Scholar
28. McCarty, R. Cross-fostering: elucidating the effects of gene environment interactions on phenotypic development. Neurosci Biobehav Rev. 2017; 73, 219–254.Google Scholar
29. Luyckx, VA, Brenner, BM. Low birth weight, nephron number, and kidney disease. Kidney Int Suppl. 2005; 97, S68–S77. https://doi.org/10.1111/j.1523-1755.2005.09712.x(97).Google Scholar
30. Moritz, KM, Wintour, EM, Black, MJ, Bertram, JF, Caruana, G. Factors influencing mammalian kidney development: implications for health in adult life. Adv Anat Embryol Cell Biol. 2008; 196, 1–78.Google Scholar
31. Hostetter, TH, Olson, JL, Rennke, HG, Venkatachalam, MA, Brenner, BM. Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. Am J Physiol. 1981; 241, F85–F93.Google Scholar
32. Simons, JL, Provoost, AP, Anderson, S, et al. Pathogenesis of glomerular injury in the fawn-hooded rat: early glomerular capillary hypertension predicts glomerular sclerosis. J Am Soc Nephrol. 1993; 3, 1775–1782.Google Scholar
33. 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
34. Fowden, AL, Giussani, DA, Forhead, AJ. Intrauterine programming of physiological systems: causes and consequences. Physiology (Bethesda). 2006; 21, 29–37.Google Scholar
35. Graignic-Philippe, R, Dayan, J, Chokron, S, Jacquet, AY, Tordjman, S. Effects of prenatal stress on fetal and child development: a critical literature review. Neurosci Biobehav Rev. 2014; 43, 137–162.Google Scholar
36. Vikse, BE, Irgens, LM, Leivestad, T, Hallan, S, Iversen, BM. Low birth weight increases risk for end-stage renal disease. J Am Soc Nephrol. 2008; 19, 151–157.Google Scholar
37. Schrier, RW. Renal volume, renin-angiotensin-aldosterone system, hypertension, and left ventricular hypertrophy in patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol. 2009; 20, 1888–1893.Google Scholar
38. Van Vliet, BN, Chafe Ll Fau-Antic, V, Antic, V, et al. Direct and indirect methods used to study arterial blood pressure. J Pharmacol Toxicol Methods. 2000; 44, 361–373.Google Scholar
39. Crispi, F, Hernandez-Andrade, E, Pelsers, MM, et al. Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses. Am J Obstet Gynecol. 2008; 199, 254.e251–254.e258.Google Scholar
40. Tomek, J, Bub, G. Hypertension-induced remodelling: on the interactions of cardiac risk factors. J Physiol. 2017; 595, 4027–4036.Google Scholar
41. Grantham, JJ, Chapman, AB, Torres, VE. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol. 2006; 1, 148–157.Google Scholar
42. Halvorson, CR, Bremmer, MS, Jacobs, SC. Polycystic kidney disease: inheritance, pathophysiology, prognosis, and treatment. Int J Nephrol Renovasc Dis. 2010; 3, 69–83.Google Scholar
43. Gretz, N, Ceccherini, I, Kranzlin, B, et al. Gender-dependent disease severity in autosomal polycystic kidney disease of rats. Kidney Int. 1995; 48, 496–500.Google Scholar
44. Silbiger, SR, Neugarten, J. The role of gender in the progression of renal disease. Adv Ren Replace Ther. 2003; 10, 3–14.Google Scholar
45. Veiras, LC, Girardi, ACC, Curry, J, et al. Sexual dimorphic pattern of renal transporters and electrolyte homeostasis. J Am Soc Nephrol . 2017; 28, 3504–3517.Google Scholar
46. Ding, A, Kalaignanasundaram, P, Ricardo, SD, et al. Chronic treatment with tempol does not significantly ameliorate renal tissue hypoxia or disease progression in a rodent model of polycystic kidney disease. Clin Exp Pharmacol Physiol. 2012; 39, 917–929.Google Scholar
47. Ow, CP, Abdelkader, A, Hilliard, LM, Phillips, JK, Evans, RG. Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease. Am J Physiol Regul Integr Comp Physiol. 2014; 307, R1207–R1215.Google Scholar
48. Canzian, F. Phylogenetics of the laboratory rat Rattus norvegicus. Genome Res. 1997; 7, 262–267.Google Scholar
49. Mrug, M, Zhou, J, Yang, C, et al. Genetic and informatic analyses implicate Kif12 as a candidate gene within the Mpkd2 locus that modulates renal cystic disease severity in the Cys1 cpk mouse. PLoS One. 2015; 10, e0135678.Google Scholar
50. Harris, PC, Torres, VE. Polycystic kidney disease. Annu Rev Med. 2009; 60, 321–337.Google Scholar
51. Singh, V. Polycystic kidney disease: a paradigm in major kidney disorders. Biochem Physiol. 2015; 4, 2.Google Scholar