Food intake and the kidney: The right amounts at the right times

Abstract

See related article on page 467. In this issue of the Journal, Lucas et al1Lucas SRR Miraglia SM Zaladek Gil F Coimbra TM Intrauterine food restriction as a determinant of nephrosclerosis.Am J Kidney Dis. 2001; 37: 467-476Abstract Full Text Full Text PDF Scopus (57) Google Scholar present compelling evidence in an animal model that maternal nutritional status during pregnancy exerts a direct effect on the development of renal disease in offspring.1Lucas SRR Miraglia SM Zaladek Gil F Coimbra TM Intrauterine food restriction as a determinant of nephrosclerosis.Am J Kidney Dis. 2001; 37: 467-476Abstract Full Text Full Text PDF Scopus (57) Google Scholar The group had shown earlier that glomeruli of infant rats from Dams deprived of adequate nutrition during pregnancy resulted in offspring with fewer renal glomeruli and larger glomeruli than offspring of Dams with good prenatal nutrition.2Lucas SR Costa Silva VL Miraglia SM Zaladek Gil F Functional and morphometric evaluation of offspring kidney after intrauterine undernutrition.Pediatr Nephrol. 1997; 11: 719-723Google Scholar The authors observed that reducing food intake during pregnancy resulted in nephrosclerosis in the offspring when they were 18 months of age. This age is well into middle age for the rat. The offspring of Dams deprived of food during pregnancy had reduced glomerular filtration rate, increased proteinuria, increased glomerulosclerosis score, tubulointerstitial nephritis, and matrix deposition, compared with control offspring whose mothers were not food-restricted during their pregnancy. In addition to providing important mechanistic insights, the authors have provided a serviceable animal model to investigate the effects of prenatal maternal nutrition on the subsequent development of renal disease in offspring. These experimental findings are also highly complimentary of recent epidemiological studies in humans. Barker et al3Barker DJP Hales CN Fall CHD Osmond C Phipps C Clark PMS Type 2 diabetes mellitus, hypertension, and hyperlipidemia (syndrome X): Relation to reduced fetal growth.Diabetologia. 1993; 36: 62-67Google Scholar, 4Barker DJP Martyn CN The maternal and infant origins of cardiovascular disease.J Epidemiol Community Health. 1992; 46: 8-11Google Scholar first proposed that intrauterine malnutrition, marked by low birth weight, predisposes persons to type 2 diabetes mellitus, hypertension, dyslipidemia, and cardiovascular disease. The extension of these observations to renal disease was provided by Nelson et al5Nelson RG Morgenstern H Bennett PH Birth weight and renal disease in Pima Indians with type 2 diabetes.Am J Epidemiol. 1998; 148: 650-656Google Scholar in the Pima Indians. The Pimas have an extremely high incidence of type 2 diabetes mellitus and the highest rate of end-stage renal disease (ESRD) in the world. Very low and very high birth weight both predisposed the Pimas to diabetes and ESRD. Hoy et al6Hoy WE Rees M Kile E Mathews JD Wang Z A new dimension to the Barker hypothesis: Low birthweight and susceptibility to renal disease.Kidney Int. 1999; 56: 1072-1077Google Scholar studied Aborigines from Australia’s Northern Territory. This population also has an exceptionally high ESRD incidence. In the Aborigines, birth weight was positively correlated with body mass index, blood pressure, and diabetes, but was inversely correlated with renal disease as reflected by the albumin/creatinine ratio. The relative risk for proteinuria in persons with low birth weight was 2.8 in the Aborigines. The authors then applied a multivariate model and showed that low birth weight, body mass index (BMI), blood pressure, and diabetes acted in concert to amplify the risk of proteinuria with increasing age. Hoy et al6Hoy WE Rees M Kile E Mathews JD Wang Z A new dimension to the Barker hypothesis: Low birthweight and susceptibility to renal disease.Kidney Int. 1999; 56: 1072-1077Google Scholar could not show a U-shaped relationship between birth weight and diabetes or ESRD risk in their population because no U (high birth weight infants) was available for study in their population. Lackland et al7Lackland DT Bendall HE Osmond C Egan BM Barker DJ Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States.Arch Intern Med. 2000; 160: 1472-1476Google Scholar have recently described such a relationship between birth weight and diabetes risk in a population from the southeastern United States. This area is commonly known as the “stroke belt” because of the inordinately high risk of stroke. South Carolina, the heart of the stroke belt, also has one of the nation’s highest ESRD rates. The authors performed a case-control study in 1,230 dialysis patients from South Carolina who had accurate measurements of birth weight. In individuals with birth weights lower than 2.5 kg, the ESRD relative risk was 1.4, compared with persons who weighed more than 3 kg at birth. The association was present for renal failure resulting from diabetes, hypertension, or other causes. The birth weight-related risk for diabetes mellitus in this study was also U shaped, while the risks for hypertension and other renal diseases were inversely linear. The relationships between birth weight and hypertension, diabetes, lipid disturbances, and cardiovascular disease are impressive. However, what about the effects of development after birth? Eriksson et al8Eriksson J Forsen T Tuomilehto J Osmond C Barker D Fetal and childhood growth and hypertension in adult life.Hypertension. 2000; 36: 790-794Google Scholar recently examined this issue. They studied a Finnish cohort of 7,086 individuals whose birth weights and subsequent development were known. They confirmed the inverse relationship between birth weight and subsequent risk for hypertension. After birth, low birth weight persons gained weight more rapidly, so that by age 7 years, they had caught up with their higher birth weight contemporaries. Postnatal weight gain was also associated with better living conditions. The authors’ findings imply that rapid weight gain and growth during childhood contribute to the risk for hypertension. The human data are compelling; however, further insights require serviceable animal models. Brenner and Chertow9Brenner BM Chertow GM Congenital oligonephropathy and the etiology of adult hypertension and progressive renal injury.Am J Kidney Dis. 1994; 23: 171-175Google Scholar have suggested that reduction in the number of nephrons at birth leads to hyperperfusion of each nephron and resulting glomerular sclerosis, further nephron death, and a cycle of increasing blood pressure and nephron death. In humans, 60% of the nephrons are laid down during the last trimester and renal development is completed by the 35th week.10Hinchliffe 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: 777-784Google Scholar Intrauterine malnutrition is associated with reduced nephrons in animals and humans.11Lucas SR Zaladek-Gil F Costa-Silva VL Miraglia SM Function and morphometric evaluation of intrauterine undernutrition on kidney development of the progeny.Braz J Med Biol Res. 1991; 24: 967-970Google Scholar, 12Hinchliffe SA Lynch MR Sargent PH Howard CV van Velzen D The effect of intrauterine growth retardation on the development of renal nephrons.Br J Obstet Gynaecol. 1992; 99: 296-301Google Scholar, 13Merlet-Benichou C Vilar J Lelievre-Pegorier M Moreau E Gilbert T Fetal nephron mass: Its control and deficit.Adv Nephrol. 1997; 26: 19-45Google Scholar Furthermore, intrauterine nutritional effects extend to other vascular beds as well. Chapman et al14Chapman N Mohamudally A Cerutti A Stanton A Sayer AA Cooper C Barker D Rauf A Evans J Wormald R Sever P Hughes A Thom S Retinal vascular network architecture in low-birth-weight men.J Hypertens. 1997; 15: 1449-1453Google Scholar observed that persons with low birth weight have a retinal arteriolar geometry characterized by narrow bifurcation angles, compared with persons with higher birth weights. This altered vascular architecture could lead to a greater mechanical work requirement for adequate perfusion. What are the mechanisms by which in utero malnutrition influences nephron development and nephron number? Effects on the hypothalamic-pituitary-adrenal axis have been implicated. Phillips et al15Phillips DI Barker DJ Fall CH Seckl JR Whorwood CB Wood PJ Walker BR Elevated plasma cortisol concentrations: A link between low birth weight and the insulin resistance syndrome?.J Clin Endocrinol Metab. 1998; 83: 757-760Google Scholar made measurements on men born between 1920 and 1930 and observed an inverse relationship between low birth weight and subsequent cortisol levels, as well as correlations between cortisol and blood pressure, glucose concentrations, triglyceride concentrations, and insulin resistance. The group has extended these observations to other populations.16Phillips DI Walker BR Reynolds RM Flanagan DE Wood PJ Osmond C Barker DJ Whorwood CB Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations.Hypertension. 2000; 35: 1301-1306Google Scholar The effects of in utero malnutrition are complex. Liver function is apparently also involved with lasting effects into adult life as a recent report on fibrinogen levels and a relationship with low birth weight indicates.17Roseboom TJ van der Meulen JH Ravelli AC Osmond C Barker DJ Bleker OP Plasma fibrinogen and factor VII concentrations in adults after prenatal exposure to famine.Br J Haematol. 2000; 111: 112-117Google Scholar Nutrition has a profound effect on gene expression, including many genes that influence growth.18Stearns MR Jackson CG Landauer JA Frye SD Hay Jr, WW Burke TJ Small for gestational age: A new insight?.Med Hypotheses. 1999; 53: 186-189Google Scholar Acidosis reduces the ability of nitric oxide synthase to generate nitric oxide from l -arginine, even if dietary intake or plasma levels of l -arginine are normal. Acidemia occurs with slow fetal growth in utero and has been implicated as a factor in the long-term consequences.19Jackson AA Langley-Evans SC McCarthy HD Nutritional influences in early life upon obesity and body proportions.Ciba Found Symp. 1996; 201 (discussion on pp 129-137 and 188-193): 118-129Google Scholar Interestingly, the age at which these influences are exerted has a pleiotropic effect on subsequent well being. The animal study by Lucas et al1Lucas SRR Miraglia SM Zaladek Gil F Coimbra TM Intrauterine food restriction as a determinant of nephrosclerosis.Am J Kidney Dis. 2001; 37: 467-476Abstract Full Text Full Text PDF Scopus (57) Google Scholar reported here and the recent human observations have documented the in utero effects of decreased nutrition.3Barker DJP Hales CN Fall CHD Osmond C Phipps C Clark PMS Type 2 diabetes mellitus, hypertension, and hyperlipidemia (syndrome X): Relation to reduced fetal growth.Diabetologia. 1993; 36: 62-67Google Scholar, 4Barker DJP Martyn CN The maternal and infant origins of cardiovascular disease.J Epidemiol Community Health. 1992; 46: 8-11Google Scholar, 5Nelson RG Morgenstern H Bennett PH Birth weight and renal disease in Pima Indians with type 2 diabetes.Am J Epidemiol. 1998; 148: 650-656Google Scholar, 6Hoy WE Rees M Kile E Mathews JD Wang Z A new dimension to the Barker hypothesis: Low birthweight and susceptibility to renal disease.Kidney Int. 1999; 56: 1072-1077Google Scholar, 7Lackland DT Bendall HE Osmond C Egan BM Barker DJ Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States.Arch Intern Med. 2000; 160: 1472-1476Google Scholar, 8Eriksson J Forsen T Tuomilehto J Osmond C Barker D Fetal and childhood growth and hypertension in adult life.Hypertension. 2000; 36: 790-794Google Scholar Eriksson et al8Eriksson J Forsen T Tuomilehto J Osmond C Barker D Fetal and childhood growth and hypertension in adult life.Hypertension. 2000; 36: 790-794Google Scholar have shown us that low birth weight individuals “catch up” rapidly, which has a bearing on their subsequent risk. Apparently, the catch up is conducted for a lifetime, since the low birth weight individuals eventually have an even greater BMI than the infants who were heavier at birth.20Hoeflich A Schmidt P Foll J Rottmann O Weber MM Kolb HJ Pirchner F Wolf E Altered growth of mice divergently selected for body weight is associated with complex changes in the growth hormone/insulin-like growth factor system.Growth Horm IGF Res. 1998; 8: 113-123Google Scholar Obesity is a major health problem and is perhaps also influenced by low birth weight. Fasting in adulthood, presumably after childbearing, has salubrious effects on aging and diminishes expression of an entire gamut of stress-related genes.21Lee CK Klopp RG Weindruch R Prolla TA Gene expression profile of aging and its retardation by caloric restriction.Science. 1999; 285: 1390-1393Google Scholar However, these benefits only occur in the presence of sufficient nutrient quality and density.22Hart RW Dixit R Seng J Turturro A Leakey JE Feuers R Duffy P Buffington C Cowan G Lewis S Pipkin J Li SY Adaptive role of caloric intake on the degenerative disease processes.Toxicol Sci. 1999; 52: S3-S12Google Scholar There is much food for thought in these studies and the public health implications are obvious.