Hostname: page-component-586b7cd67f-dsjbd Total loading time: 0 Render date: 2024-11-28T15:22:12.899Z Has data issue: false hasContentIssue false
  • English
  • Français

Proteinuria in aging rats due to low-protein diet during mid-gestation

Published online by Cambridge University Press:  18 December 2009

J. A. Joles ,
D. V. Sculley  and
S. C. Langley-Evans
J. A. Joles*
Affiliation:
Department of Nephrology, University Medical Center, Utrecht, Netherlands
D. V. Sculley
Affiliation:
Department of Nutrition, School of Biosciences, Nottingham, UK
S. C. Langley-Evans
Affiliation:
Department of Nutrition, School of Biosciences, Nottingham, UK
*
Address for correspondence: J. A. Joles, D.V.M., Department of Nephrology and Hypertension F03.223, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Nephrogenesis in the rat starts mid-gestation and continues into lactation. Maternal low protein (LP) intake leads to renal injury in rats and associates with mild renal injury in humans. We hypothesized that LP during early nephrogenesis or throughout gestation would induce more renal injury in rat offspring than when LP was only present before nephrogenesis. Pregnant rats were fed LP diet (9% casein) at early gestation (LPE, day 0–7), mid (LPM, day 8–14), late (LPL, day 15–22) or throughout gestation (LPA, day 0–22) and compared to controls on 18% casein diet. Offspring were studied at 18 months. Renal injury was assessed by 24 h proteinuria, plasma urea, antioxidant enzyme activities, and apoptosis (Bax/Bcl2). Proteinuria was higher in LPM males and LPE and LPM females. In LPM males glutathione peroxidase activity was lower, while in LPE males catalase activity was higher. Antioxidants were not much affected in females. Bax expression was higher in LPM males and females, while Bcl2 expression was higher in LPA females. Thus even before nephrogenesis (day 0–7), LP impacted on renal integrity in adult life, while LP during a later phase (day 15–22) or throughout gestation had less effect. In summary, for aging rat kidney LP poses the greatest threat when restricted to early nephrogenesis.

Keywords

aging rats, antioxidant enzymes, fetal programming, low-protein diet, proteinuria
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 1 , Issue 1 , February 2010 , pp. 75 - 83
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Guron, G, Friberg, P. An intact renin-angiotensin system is a prerequisite for normal renal development. J Hypertens. 2000; 18, 123–137.CrossRefGoogle ScholarPubMed
2.Langley-Evans, SC, Welham, SJ, Jackson, AA. Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci. 1999; 64, 965–974.Google Scholar
3.Nuyt, AM, Alexander, BT. Developmental programming and hypertension. Curr Opin Nephrol Hypertens. 2009; 18, 144–152.CrossRefGoogle ScholarPubMed
4.Nwagwu, MO, Cook, A, Langley-Evans, SC. Evidence of progressive deterioration of renal function in rats exposed to a maternal low-protein diet in utero. Br J Nutr. 2000; 83, 79–85.CrossRefGoogle ScholarPubMed
5.Regina, S, Lucas, R, Miraglia, SM, Zaladek Gil, F, Machado Coimbra, T. Intrauterine food restriction as a determinant of nephrosclerosis. Am J Kidney Dis. 2001; 37, 467–476.Google ScholarPubMed
6.Vehaskari, VM. Developmental origins of adult hypertension: new insights into the role of the kidney. Pediatr Nephrol. 2007; 22, 490–495.Google Scholar
7.Painter, RC, Roseboom, TJ, van Montfrans, GA, et al. Microalbuminuria in adults after prenatal exposure to the Dutch famine. J Am Soc Nephrol. 2005; 16, 189–194.CrossRefGoogle Scholar
8.McMillen, IC, Robinson, JS. Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev. 2005; 85, 571–633.CrossRefGoogle ScholarPubMed
9.Jennings, BJ, Ozanne, SE, Dorling, MW, Hales, CN. Early growth determines longevity in male rats and may be related to telomere shortening in the kidney. FEBS Lett. 1999; 448, 4–8.CrossRefGoogle ScholarPubMed
10.Langley-Evans, SC, Sculley, DV. The association between birth weight and longevity in the rat is complex and modulated by maternal protein intake during fetal life. FEBS Lett. 2006; 580, 4150–4153.Google Scholar
11.Aihie Sayer, A, Dunn, R, Langley-Evans, SC, Cooper, C. Prenatal exposure to a maternal low protein diet shortens life span in rats. Gerontology. 2001; 47, 9–14.Google Scholar
12.Langley-Evans, SC. Nutritional programming of disease: unraveling the mechanism. J Anat. 2009; 215, 36–51.CrossRefGoogle ScholarPubMed
13.Mallinson, JE, Sculley, DV, Craigon, J, et al. Fetal exposure to a maternal low-protein diet during mid-gestation results in muscle-specific effects on fiber type composition in young rats. Br J Nutr. 2007; 98, 292–299.Google Scholar
14.Bellinger, L, Sculley, DV, Langley-Evans, SC. Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats. Int J Obes (Lond). 2006; 30, 729–738.Google Scholar
15.Baylis, C. Age-dependent glomerular damage in the rat. Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a primary risk factor. J Clin Invest. 1994; 94, 1823–1829.CrossRefGoogle ScholarPubMed
16.Baylis, C. Changes in renal hemodynamics and structure in the aging kidney; sexual dimorphism and the nitric oxide system. Exp Gerontol. 2005; 40, 271–278.CrossRefGoogle ScholarPubMed
17.Langley-Evans, SC, Phillips, GJ, Jackson, AA. Fetal exposure to low protein maternal diet alters the susceptibility of young adult rats to sulfur dioxide-induced lung injury. J Nutr. 1997; 127, 202–209.Google ScholarPubMed
18.Langley-Evans, SC, Sculley, DV. Programming of hepatic antioxidant capacity and oxidative injury in the ageing rat. Mech Ageing Dev. 2005; 126, 804–812.CrossRefGoogle ScholarPubMed
19.Langley-Evans, SC, Wood, S, Jackson, AA. Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition. Ann Nutr Metab. 1995; 39, 28–35.CrossRefGoogle ScholarPubMed
20.Langley, SC, Seakins, M, Grimble, RF, Jackson, AA. The acute phase response of adult rats is altered by in utero exposure to maternal low-protein diets. J Nutr. 1994; 124, 1588–1596.CrossRefGoogle ScholarPubMed
21.Blezer, EL, Schurink, M, Nicolay, K, et al. Proteinuria precedes cerebral edema in stroke-prone rats: a magnetic resonance imaging study. Stroke. 1998; 29, 167–174.CrossRefGoogle ScholarPubMed
22.Thomas, L. Clinical Laboratory Diagnostics, 1st edn, 1998. TH-Books Verlagsgesellschaft: Frankfurt, Germany.Google Scholar
23.Burtis, CA, Ashwood, ER, editors. Tietz Textbook of Clinical Chemistry, 3rd edn, 1999. WB Saunders Company: PA, USA.Google Scholar
24.Aebi, H. Catalase in vitro. Methods Enzymol. 1984; 105, 121–126.CrossRefGoogle ScholarPubMed
25.Winterbourn, CC, Hawkins, RE, Brian, M, Carrell, RW. The estimation of red cell superoxide dismutase activity. J Lab Clin Med. 1975; 85, 337–341.Google ScholarPubMed
26.Langley, SC, Kelly, FJ. Differing response of the glutathione system to fasting in neonatal and adult guinea pigs. Biochem Pharmacol. 1992; 44, 1489–1494.CrossRefGoogle ScholarPubMed
27.Tietze, F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969; 27, 502–522.Google Scholar
28.Thomas, SE, Anderson, S, Gordon, KL, et al. Tubulointerstitial disease in aging: evidence for underlying peritubular capillary damage, a potential role for renal ischemia. J Am Soc Nephrol. 1998; 9, 231–242.CrossRefGoogle Scholar
29.Petry, CJ, Jennings, BJ, James, LA, Hales, CN, Ozanne, SE. Suckling a protein-restricted rat dam leads to diminished albuminuria in her male offspring in adult life: a longitudinal study. BMC Nephrol. 2006; 7, 14.CrossRefGoogle Scholar
30.Welham, SJ, Wade, A, Woolf, AS. Protein restriction in pregnancy is associated with increased apoptosis of mesenchymal cells at the start of rat metanephrogenesis. Kidney Int. 2002; 61, 1231–1242.CrossRefGoogle ScholarPubMed
31.Welham, SJ, Riley, PR, Wade, A, Hubank, M, Woolf, AS. Maternal diet programs embryonic kidney gene expression. Physiol Genomics. 2005; 22, 48–56.Google Scholar
32.Roberts, CK, Barnard, RJ, Sindhu, RK, et al. Oxidative stress and dysregulation of NAD(P)H oxidase and antioxidant enzymes in diet-induced metabolic syndrome. Metabolism. 2006; 55, 928–934.CrossRefGoogle ScholarPubMed
33.Zhan, CD, Sindhu, RK, Pang, J, Ehdaie, A, Vaziri, ND. Superoxide dismutase, catalase and glutathione peroxidase in the spontaneously hypertensive rat kidney: effect of antioxidant-rich diet. J Hypertens. 2004; 22, 2025–2033.CrossRefGoogle ScholarPubMed
34.Tomat, AL, Inserra, F, Veiras, L, et al. Moderate zinc restriction during fetal and postnatal growth of rats: effects on adult arterial blood pressure and kidney. Am J Physiol Regul Integr Comp Physiol. 2008; 295, R543–R549.CrossRefGoogle ScholarPubMed
35.Tarry-Adkins, JL, Ozanne, SE, Norden, A, Cherif, H, Hales, CN. Lower antioxidant capacity and elevated p53 and p21 may be a link between gender disparity in renal telomere shortening, albuminuria, and longevity. Am J Physiol Renal Physiol. 2006; 290, F509–F516.CrossRefGoogle ScholarPubMed
36.Eddy, AA. Interstitial nephritis induced by protein-overload proteinuria. Am J Pathol. 1989; 135, 719–733.Google ScholarPubMed
37.Tapia, E, Sánchez-González, DJ, Medina-Campos, ON, et al. Treatment with pyrrolidine dithiocarbamate improves proteinuria, oxidative stress, and glomerular hypertension in overload proteinuria. Am J Physiol Renal Physiol. 2008; 295, F1431–F1439.CrossRefGoogle ScholarPubMed
38.Christensen, EI, Birn, H, Rippe, B, Maunsbach, AB. Controversies in nephrology: renal albumin handling, facts, and artifacts!. Kidney Int. 2007; 72, 1192–1194.Google Scholar
39.Comper, WD, Russo, LM. The glomerular filter: an imperfect barrier is required for perfect renal function. Curr Opin Nephrol Hypertens. 2009; 18, 336–342.CrossRefGoogle ScholarPubMed
40.Tryggvason, K, Patrakka, J, Wartiovaara, J. Hereditary proteinuria syndromes and mechanisms of proteinuria. N Engl J Med. 2006; 354, 1387–1401.Google Scholar
41.Pugliese, G, Ricci, C, Iacobini, C, et al. Glomerular barrier dysfunction in glomerulosclerosis – resistant Milan rats with experimental diabetes: the role of renal hemodynamics. J Pathol. 2007; 213, 210–218. Erratum: The Journal of Pathology. 2007; 213, 218.Google Scholar
42.Percy, CJ, Brown, L, Power, DA, Johnson, DW, Gobe, GC. Obesity and hypertension have differing oxidant handling molecular pathways in age-related chronic kidney disease. Mech Ageing Dev. 2009; 130, 129–138.Google Scholar
43.Thomas, ME, Brunskill, NJ, Harris, KP, et al. Proteinuria induces tubular cell turnover: a potential mechanism for tubular atrophy. Kidney Int. 1999; 55, 890–898.CrossRefGoogle ScholarPubMed
44.Singh, DK, Winocour, P, Farrington, K. Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol. 2008; 4, 216–226.CrossRefGoogle ScholarPubMed
45.Silbiger, SR, Neugarten, J. The impact of gender on the progression of chronic renal disease. Am J Kidney Dis. 1995; 25, 515–533.CrossRefGoogle ScholarPubMed
46.Woods, LL, Ingelfinger, JR, Rasch, R. Modest maternal protein restriction fails to program adult hypertension in female rats. Am J Physiol Regul Integr Comp Physiol. 2005; 289, R1131–R1136.Google Scholar
47.Maduwegedera, D, Kett, MM, Flower, RL, et al. Sex differences in postnatal growth and renal development in offspring of rabbit mothers with chronic secondary hypertension. Am J Physiol Regul Integr Comp Physiol. 2007; 292, R706–R714.Google Scholar
48.Gardner, DS, Van Bon, BW, Dandrea, J, et al. Effect of periconceptional undernutrition and gender on hypothalamic-pituitary-adrenal axis function in young adult sheep. J Endocrinol. 2006; 190, 203–212.CrossRefGoogle ScholarPubMed
49.McMullen, S, Langley-Evans, SC. Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms. Am J Physiol Regul Integr Comp Physiol. 2005; 288, R85–R90.Google Scholar
50.Langley-Evans, SC, Welham, SJ, Sherman, RC, Jackson, AA. Weanling rats exposed to maternal low-protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clin Sci (Lond). 1996; 91, 607–615.CrossRefGoogle ScholarPubMed
51.Erhuma, A, Salter, AM, Sculley, DV, Langley-Evans, SC, Bennett, AJ. Prenatal exposure to a low-protein diet programs disordered regulation of lipid metabolism in the aging rat. Am J Physiol Endocrinol Metab. 2007; 292, E1702–E1714.CrossRefGoogle ScholarPubMed
52.Gopalakrishnan, GS, Gardner, DS, Dandrea, J, et al. Influence of maternal pre-pregnancy body composition and diet during early-mid pregnancy on cardiovascular function and nephron number in juvenile sheep. Br J Nutr. 2005; 94, 938–947.Google Scholar
53.Hinchliffe, SA, Sargent, PH, Howard, CV, Chan, YF, van Velzen, D. Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the dissector method and Cavalieri principle. Lab Invest. 1991; 64, 777–784.Google Scholar
54.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, 371–384.CrossRefGoogle ScholarPubMed