Weight for Gestational Age as a Baseline Predictor of Kidney Function in Adulthood
2008; Elsevier BV; Volume: 51; Issue: 1 Linguagem: Inglês
10.1053/j.ajkd.2007.11.004
ISSN1523-6838
Autores Tópico(s)Neonatal Respiratory Health Research
ResumoRelated Article, p. 10 Related Article, p. 10 While there is persuasive evidence for an association between lower birth weight and future cardiovascular disease in humans,1Barker D.J.P. Winter P.D. Osmond C. Margetts B. Simmonds S.J. Weight in infancy and death from ischemic heart disease.Lancet. 1989; 2: 577-580Abstract PubMed Scopus (2630) Google Scholar correlations between perinatal events, birth weight, and kidney disease in adult life have been more difficult to establish.2Hughson M.D. Low birth weight and kidney function: Is there a relationship and is it determined by the intrauterine environment?.Am J Kidney Dis. 2007; 50: 531-534Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Experimental models demonstrate that intrauterine growth restriction is associated with albuminuria and decreased renal function in adult life, but longitudinal data in humans have been sparse. In this month's issue of AJKD, a report by Hallan et al3Hallan S. Euser A.M. Irgens L.M. Finken M.J.J. Homen J. Dekker F.W. Effect of intrauterine growth restriction on kidney function at young adult age: The Nord Trøndelag Health (HUNT 2) Study.Am J Kidney Dis. 2008; 51: 10-20Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar from the Nord Trøndelag Health 2 (HUNT 2) study suggests that persons with relatively lower birth weights at term display mild decreases in renal function at age 20 to 30 years. The HUNT 2 study,4Hallan S. Astor B. Lydersen S. Estimating glomerular filtration rate in the general population: the second Health Survey of Nord-Trondelag (HUNT II).Nephrol Dial Transplant. 2006; 21: 1525-1533Crossref PubMed Scopus (55) Google Scholar carried out from 1995 to 1997, accessed data from the Medical Birth Registry of Norway, which included birth weight, gestational age, and maternal and perinatal risk factors, and then linked the information to current health measures among study participants. The present report from the HUNT 2 study enlisted participants aged 20 to 30 years (N = 7,457) who then underwent renal functional assessments that could be correlated with status at birth. Glomerular filtration was estimated using 2 accepted methods (described in5Statistics Norway. Health: Life and Death.http://www.ssb.no/english/subjects/00/norge_en/helse_en/main.htmlDate: 2007Google Scholar), the Cockcroft-Gault method and the isotope dilution mass spectrometry–traceable 4-variable Modification of Diet in Renal Disease (MDRD) Study equation. The authors defined results for estimated glomerular filtration rate (eGFR) that fell below sex-specific 10th percentiles as signifying "low-normal" kidney function, representing an eGFR of less than 92 mL/min/1.73 m2 (1.53 mL/s/1.73 m2) in men and less than 85 to 86 mL/min/1.73 m2 (1.42-1.43 mL/s/1.73 m2) in women. They employed standard deviation scores to adjust for gestational age so that, based on birth weights, participants were labeled as having been appropriate for gestational age (10th-90th percentile) if birth weight-standard deviation score (BW-SDS) was −1.3 to 1.3, small (3rd-10th percentile) if BW-SDS was −2.0 to −1.3, and very small (<3rd percentile) if BW-SDS was lower than −2.0 at birth. The results of these studies and calculations demonstrated that among men aged 20 to 30, lower birth weight was associated with increased odds of having low-normal kidney function. This association was less robust for women. Importantly, the results imply that low birth weight might constitute a health risk, since life expectancy in Norway is high (at the time of HUNT 2, it was approximately 75 years for men and 82 for women),5Statistics Norway. Health: Life and Death.http://www.ssb.no/english/subjects/00/norge_en/helse_en/main.htmlDate: 2007Google Scholar and the participants would be expected to live another 50 years or so, thus having a higher ultimate chance of developing advanced stages of chronic kidney disease. The data set from the HUNT 2 study is particularly valuable, owing to the large number of participants and the well-documented early life data. Yet, there are a number of limitations inherent in the data, some of which are highlighted in the paper by the investigators themselves. First, only 49% of the identified cohort participated in the study, though the authors state that when they compared both maternal and neonatal data from both participants and nonparticipants, they observed no differences between the groups. Second, they note that there may be special considerations in estimating GFR in growth-restricted persons that could not be addressed. Additionally, urinary albumin excretion rate was not generally available among the study participants at age 20 to 30; thus, that important marker could only be used in evaluating the potential differences in a subset of participants. A further limitation is that those participants who had been classified as small for gestational age constituted a minority of the total. A more concerning issue is that the actual diagnosis of intrauterine growth restriction at birth was based on limited data. Repeated measures of fetal growth by ultrasonography would have been optimal, but this technology was not widely applied or recorded when the participants were in utero. The concept of size for gestational age is based on size at birth and does not account for periods of suboptimal growth not reflected in the final birth weight. Even with all of these limitations, the HUNT 2 study appears to be the largest of its type and adds important information to the literature on intrauterine milieu and its effect on renal endowment. As with the HUNT 2 study, other attempts to associate being small for gestational age at birth to subsequent alterations in GFR or to microalbuminuria or frank proteinuria have met with methodological problems. Hoy et al were among the first to point out an increased risk of albuminuria with lower birth weight, reporting that among 317 adults aged 20 to 38 years at the time of the study, the odds ratio was 2.82 (confidence interval, 1.24-6.31) for having proteinuria among those who had weight at birth of under 2.5 kg.6Hoy W.E. Rees M. Kile E. Mathews J.D. Zhang Z. A new dimension to the Barker hypothesis: low birth weight and susceptibility to renal disease.Kidney Int. 1999; 56: 1072-1077Crossref PubMed Scopus (286) Google Scholar Among the oldest cohorts available for evaluation are survivors among the Dutch famine cohort, persons who were born towards the end of World War II, when food was exceedingly scarce in areas of The Netherlands. Recently, Painter et al determined albumin-to-creatinine ratios, as well as eGFR, in 724 individuals who were born at term during that famine, and who were 48 to 53 years at the time of study.7Painter R.C. Roseboom T.J. van Montfrans G.A. et al.Microalbuminuria in adults after prenatal exposure to the Dutch famine.J Am Soc Nephrol. 2005; 16: 189-194Crossref PubMed Scopus (185) Google Scholar While there were not significant differences in creatinine clearances, 12% of those exposed to famine as fetuses in midgestation had microalbuminuria as compared to 7% of those who had not been exposed to famine. As microalbuminuria predicts decrease in renal function, one might speculate that renal function in this cohort might, in future, deteriorate more quickly in those who were exposed to famine conditions while in utero. A report by Yudkin et al examined birth weight and microalbuminuria in 2 smaller cohorts.8Yudkin J.S. Phillips D.I. Stanner S. Proteinuria and progressive renal disease: birth weight and microalbuminuria.Nephrol Dial Transplant. 1997; 12: 10-13PubMed Google Scholar One cohort consisted of 236 men and women from Preston in the United Kingdom whose recorded birth weights were examined when they were 46 to 54 years of age; while 11 had microalbuminuria, there were no significant differences in either birth weight or ponderal index at birth between those with and without microalbuminuria (P = 0.20 for birth weight and P = 0.09 for ponderal index at birth). The other cohort in the Yudkin et al paper consisted of survivors of the Siege of Leningrad.8Yudkin J.S. Phillips D.I. Stanner S. Proteinuria and progressive renal disease: birth weight and microalbuminuria.Nephrol Dial Transplant. 1997; 12: 10-13PubMed Google Scholar There were 98 persons who had been exposed to starvation in utero (as fetuses of women who survived the siege) and 124 exposed to starvation in infancy; these 2 groups were compared to 62 persons born concurrently in an area geographically outside the siege. There were no significant differences in daytime or nighttime albumin excretion rates between these groups. Further, a study by Johnson et al has failed to show a relationship between birth weight and microalbuminuria.9Johnsen S.P. Sørensen H.T. Thulstrup A.M. Nørgård B. Engberg M. Lauritzen T. Fetal growth and urinary albumin excretion among middle-aged Danes.Scand J Urol Nephrol. 2001; 35: 314-318Crossref PubMed Scopus (8) Google Scholar Another measure of the influence of intrauterine and perinatal factors on future renal function is to look directly at the number of nephrons. Since there is no way to obtain such data without a direct examination of renal tissue, available information derives from study of autopsy material. This information suggests, first, that different population groups have a variable number of nephrons; human kidneys have now been documented to contain from about 200,000 to over 2 million nephrons each.10Merlet-Benichou C. Gilbert T. Vilar J. Moreau E. Freund N. Lelièvre-Pégorier M. Nephron number: Variability is the rule.Lab Invest. 1999; 79: 515-527PubMed Google Scholar, 11Hughson M. Farris III, A.B. Douglass-Denton R. Hoy W.E. Bertram J.F. Glomerular number and size in autopsy kidneys: the relationship to birth weight.Kidney Int. 2003; 63: 2113-2122Crossref PubMed Scopus (626) Google Scholar, 12Hughson M.D. Douglass-Denton R. Bertram J.F. Hoy W.E. Hypertension, glomerular number, and birth weight in African Americans and white subjects in the Southeastern United States.Kidney Int. 2006; 96: 671-678Crossref Scopus (254) Google Scholar However, only a limited number of studies link documented birth weight or intrauterine growth restriction to the number of nephrons. For example, Hinchcliffe et al examined kidneys of 6 stillborn infants who suffered marked growth restriction, and compared those with 8 normal-weight stillborn infants, as well as with a control group of appropriate-sized infants who had died subsequent to birth.13Hinchliffe S.A. Lynch M.R. Sargent P.H. Howard C.V. Van Velzen D. The effect of intrauterine growth retardation on the development of renal nephrons.Br J Obstet Gynaecol. 1992; 99: 296-301Crossref PubMed Scopus (510) Google Scholar There were significantly fewer glomeruli in the growth-restricted stillborns. More recently, Rodriquez et al reported similar findings.14Rodríguez M.M. Gómez A.H. Abitbol C.L. Chandar J.J. Duara S. Zilleruelo G.E. Histomorphometric analysis of postnatal glomerulogenesis in extremely preterm infants.Pediatr Dev Pathol. 2004; 7: 17-25Crossref PubMed Scopus (421) Google Scholar Hoy et al recently were able to obtain glomerular numbers in 19 Aboriginal people and to compare them to 24 non-Aboriginal people who died and had autopsies for forensic reasons.15Hoy W.E. Hughson M.D. Singh G.R. Douglas-Denton R. Bertram J.F. Reduced nephron number and glomerulomegaly in Australian Aborigines: A group at high risk for renal disease and hypertension.Kidney Int. 2006; 70: 104-110Crossref PubMed Scopus (213) Google Scholar There were an estimated 400,000 fewer glomeruli in Aboriginal persons (200,000 fewer per kidney) and evidence of hyperfiltration, in that glomeruli were larger. While that study did not examine GFR or protein excretion, other studies have indicated that there is much more chronic renal failure among Aboriginal people. Hypertension has been associated with having fewer glomeruli, based on limited human data. Keller et al16Keller G. Zimmer G. Mall G. Ritz E. Amann K. Nephron number in patients with primary hypertension.N Engl J Med. 2003; 348: 101-108Crossref PubMed Scopus (924) Google Scholar carried out careful assessment of glomerular size and number, comparing the results of 20 persons who died in accidents, half of whom had a history of hypertension and half of whom were normotensive. The glomerular number was smaller but individual glomerular size larger among those reported to have had hypertension during life. However, the Keller et al study16Keller G. Zimmer G. Mall G. Ritz E. Amann K. Nephron number in patients with primary hypertension.N Engl J Med. 2003; 348: 101-108Crossref PubMed Scopus (924) Google Scholar included limited clinical data, and no data about birth weight. Another approach has been to examine people with established end-stage renal disease and look back at their birth weight. For example, Lackland et al identified patients via the Southeastern Kidney Council in Raleigh, North Carolina who were undergoing dialysis from 1991 to 1996.17Lackland D.T. Bendall H.E. Osmond C. Egan B.M. Barker D.J. Low birth weights contribute to high rates of early-onset chronic renal failure in the Southeastern United States.Arch Intern Med. 2000; 160: 1472-1476Crossref PubMed Scopus (322) Google Scholar Birth weights were then obtained for those cases born in 1950 and later (N = 1,230), and for twice the number of control patients without renal failure (N = 2,460). The authors reported that lower birth weight was associated with a higher risk of developing end-stage renal disease. Further, Lackland et al reported that if a person's birth weight was less than 2.5 kg, the odds ratio for developing end-stage renal disease was 1.4 (95% confidence interval, 1.1-1.8) as compared to those who weighed 3 to 3.5 kg. Being premature per se carries a variety of increased risks, some of which are relevant to future renal function, as suggested in a study recently reported in AJKD from the Project on Prematures and Small for Gestational Age Infants (POPS), which examines a Dutch birth cohort from 1983.18Keijzer-Veen M.G. Kleinveld H.A. Lequin M.H. et al.Renal function and size at young adult age after intrauterine growth restriction and very premature birth.Am J Kidney Dis. 2007; 50: 542-551Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar That study compared a control group of 30 people who had been born at term to 2 groups who had been very premature (<32 weeks' gestation) infants: 23 prematures who were small for gestational age and 29 prematures who were appropriate for gestational age. Both groups of former premature infants had lower renal volumes and higher systolic blood pressure at age 20 years than did controls, suggesting that renal size and systolic blood pressure were negatively affected by prematurity. Importantly, the study examined both baseline renal function and measures of renal functional reserve. However, the results on renal function either did not differ significantly between the groups, or showed borderline significance. As the editorialist noted, the participant numbers in each group were modest, and the data might be variously interpreted. Thus, direct data on former premature infants would seem, in early adulthood, to be suggestive yet open to question. The HUNT 2 study and others like it hint that in utero and perinatal events influence renal outcome, yet longitudinal studies that are more complete may be required before the level of influence is clear. Improved methodology is needed for in vivo estimation of glomerular number and volume, as are widely applicable methods for determining renal functional reserve. Support: None. Financial Disclosure: None. Effect of Intrauterine Growth Restriction on Kidney Function at Young Adult Age: The Nord Trøndelag Health (HUNT 2) StudyAmerican Journal of Kidney DiseasesVol. 51Issue 1PreviewThe hypothesis of intrauterine origin of adult disease is debated. We tested whether intrauterine growth restriction is associated with later kidney function. Full-Text PDF
Referência(s)