Abstract
A high protein intake results in increased kidney growth and glomerular filtration rate in human adults and young rats. It is unknown whether kidney size in young infants is influenced by increased protein intake in formula-fed compared with breast-fed infants. We investigated the effect of formula versus breast feeding on kidney growth in a cohort of 631 healthy children examined at birth, and at 3 and 18 months of age. Kidney size was determined by ultrasonography and related to gender, age, body size, and feeding category (fully breast fed, partially breast fed, or fully formula fed at 3 months). Serum urea nitrogen, serum creatinine, and estimated creatinine clearance were measured at 3 months of age. Kidney growth and serum urea nitrogen were significantly increased in partially or fully formula-fed 3-month-old infants. This effect was more pronounced in boys than in girls. The changes in relative kidney size were temporary, as they did not persist at 18 months of age, when all children received a normal mixed diet. The immediate renal effects of formula feeding should be taken into consideration for recommendations concerning infant feeding. Whether there are any long-term effects of early increased protein intake on later kidney function remains to be seen.
Similar content being viewed by others
References
Jakobsson B, Celsi G, Lindblad BS, Aperia A (1987) Influence of different protein intake on renal growth in young rats. Acta Paediatr Scand 76:293–299
Michaelsen KF (1997) Nutrition and growth during infancy. The Copenhagen Cohort Study. Acta Paediatr [Suppl] 420:1–36
Janas LM, Picciano MF, Hatch TF (1985) Indices of protein metabolism in term infants fed human milk, whey-predominant formula, or cow’s milk formula. Pediatrics 75:775–784
Davies DP, Saunders R (1973) Blood urea. Normal values in early infancy related to feeding practices. Arch Dis Child 48:563–565
Axelsson IE, Jakobsson I, Raiha NC (1988) Formula with reduced protein content: effects on growth and protein metabolism during weaning. Pediatr Res 24:297–301
Raiha N, Minoli I, Moro G (1986) Milk protein intake in the term infant. I. Metabolic responses and effects on growth. Acta Paediatr Scand 75:881–886
Jarvenpaa AL, Raiha NC, Rassin DK, Gaull GE (1982) Milk protein quantity and quality in the term infant. I. Metabolic responses and effects on growth. Pediatrics 70:214–220
Raiha N, Minoli I, Moro G, Bremer HJ (1986) Milk protein intake in the term infant. II. Effects on plasma amino acid concentrations. Acta Paediatr Scand 75:887–892
Axelsson I, Borulf S, Raiha N (1987) Protein intake during weaning. II. Metabolic responses. Acta Paediatr Scand 76:457–462
Jarvenpaa AL, Rassin DK, Raiha NC, Gaull GE (1982) Milk protein quantity and quality in the term infant. II. Effects on acidic and neutral amino acids. Pediatrics 70:221–230
Cochran ST, Pagani JJ, Barbaric ZL (1979) Nephromegaly in hyperalimentation. Radiology 130:603–606
Skov AR, Toubro S, Bulow J, Krabbe K, Parving HH, Astrup A (1999) Changes in renal function during weight loss induced by high vs low-protein low-fat diets in overweight subjects. Int J Obes Relat Metab Disord 23:1170–1177
Schmidt IM, Main KM, Damgaard IN, Mau C, Haavisto AM, Chellakooty M, Boisen KA, Petersen JH, Scheike T, Olgaard K (2004) Kidney growth in 717 healthy children aged 0–18 months: a longitudinal cohort study. Pediatr Nephrol 19:992–1003
Schmidt IM, Chellakooty M, Haavisto AM, Boisen KA, Damgaard IN, Steendahl U, Toppari J, Skakkebaek NE, Main KM (2002) Gender difference in breast tissue size in infancy: correlation with serum estradiol. Pediatr Res 52:682–686
Chellakooty M, Schmidt IM, Haavisto AM, Boisen KA, Damgaard IN, Mau C, Petersen JH, Juul A, Skakkebaek NE, Main KM (2003) Inhibin A, inhibin B, follicle-stimulating hormone (FSH), lutenizing hormone (LH), estradiol and sex hormone-binding globulin (SHBG) levels in 473 healthy infant girls. J Clin Endocrinol Metab 88:3515–3520
Boisen KA, Kaleva M, Main KM, Virtanen HE, Haavisto AM, Schmidt IM, Chellakooty M, Damgaard IN, Mau C, Reunanen M, Skakkebaek NE, Toppari J (2004) Difference in prevalence of congenital cryptorchidism in infants between two Nordic countries. Lancet 363:1264–1269
Larsen T (2001) Intrauterine growth restriction—identification, correlation and causation evaluated by use of ultrasound. Dan Med Bull 48:256–274
Du Bois D, Du Bois EF (1916) A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 17:863–871
Zenkl M, Egghart G, Muller M (1990) The normal kidney size in children. An ultrasound study. Urologe A 29:32–38
Michaelsen KF, Pedersen SB, Skafte L, Jaeger P, Peitersen B (1988) Infrared analysis for determining macronutrients in human milk. J Pediatr Gastroenterol Nutr 7:229–235
Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34:571–590
Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz AT, Eknoyan G, Levey AS (2003) National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative clinical practice guidelines for chronic kidney disease in children and adolescents: evaluation, classification, and stratification. Pediatrics 111:1416–1421
MacKay LL, MacKay E, Addis T (1931) Factors which determine renal weight. XII. The nitrogen intake as varied by the addition of urea to the diet. J Nutr 4:479–483
Hammond KA, Janes DN (1998) The effects of increased protein intake on kidney size and function. J Exp Biol 201:2081–2090
Murray BM, Campos SP, Schoenl M, MacGillivray MH (1993) Effect of dietary protein intake on renal growth: possible role of insulin-like growth factor-I. J Lab Clin Med 122:677–685
Fomon SJ (1991) Requirements and recommended dietary intakes of protein during infancy. Pediatr Res 30:391–395
King AJ, Levey AS (1993) Dietary protein and renal function. J Am Soc Nephrol 3:1723–1737
Manz F, Remer T, Decher-Spliethoff E, Hohler M, Kersting M, Kunz C, Lausen B (1995) Effects of a high protein intake on renal acid excretion in bodybuilders. Z Ernahrungswiss 34:10–15
Herin P, Zetterstrom R (1987) Studies in renal response to various protein intakes in preterm infants. Acta Paediatr Scand 76:447–452
Chan AY, Cheng ML, Keil LC, Myers BD (1988) Functional response of healthy and diseased glomeruli to a large, protein-rich meal. J Clin Invest 81:245–254
Troell S, Berg U, Johansson B, Wikstad I (1988) Comparison between renal parenchymal sonographic volume, renal parenchymal urographic area, glomerular filtration rate and renal plasma flow in children. Scand J Urol Nephrol 22:207–214
Mogensen CE, Andersen MJ (1973) Increased kidney size and glomerular filtration rate in early juvenile diabetes. Diabetes 22:706–712
Ladefoged J, Pedersen F (1968) Relationship between roentgenological size of the kidney and the kidney function. J Urol 99:239–240
Potter D, Jarrah A, Sakai T, Harrah J, Holliday MA (1969) Character of function and size in kidney during normal growth of rats. Pediatr Res 3:51–59
Meek RL, Cooney SK, Flynn SD, Chouinard RF, Poczatek MH, Murphy-Ullrich JE, Tuttle KR (2003) Amino acids induce indicators of response to injury in glomerular mesangial cells. Am J Physiol Renal Physiol 285:F79–F86
Levey AS, Greene T, Beck GJ, Caggiula AW, Kusek JW, Hunsicker LG, Klahr S (1999) Dietary protein restriction and the progression of chronic renal disease: what have all of the results of the MDRD study shown? Modification of Diet in Renal Disease Study Group. J Am Soc Nephrol 10:2426–2439
Knight EL, Stampfer MJ, Hankinson SE, Spiegelman D, Curhan GC (2003) The impact of protein intake on renal function decline in women with normal renal function or mild renal insufficiency. Ann Intern Med 138:460–467
Hostetter TH, Meyer TW, Rennke HG, Brenner BM (1986) Chronic effects of dietary protein in the rat with intact and reduced renal mass. Kidney Int 30:509–517
Hanson LA, Korotkova M, Haversen L, Mattsby-Baltzer I, Hahn-Zoric M, Silfverdal SA, Strandvik B, Telemo E (2002) Breast-feeding, a complex support system for the offspring. Pediatr Int 44:347–352
Fall CH, Barker DJ, Osmond C, Winter PD, Clark PM, Hales CN (1992) Relation of infant feeding to adult serum cholesterol concentration and death from ischaemic heart disease. BMJ 304:801–805
Wilson AC, Forsyth JS, Greene SA, Irvine L, Hau C, Howie PW (1998) Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study. BMJ 316:21–25
Taittonen L, Nuutinen M, Turtinen J, Uhari M (1996) Prenatal and postnatal factors in predicting later blood pressure among children: cardiovascular risk in young Finns. Pediatr Res 40:627–632
Pettitt DJ, Forman MR, Hanson RL, Knowler WC, Bennett PH (1997) Breastfeeding and incidence of non-insulin-dependent diabetes mellitus in Pima Indians. Lancet 350:166–168
Oudar O, Elger M, Bankir L, Ganten D, Ganten U, Kriz W (1991) Differences in rat kidney morphology between males, females and testosterone-treated females. Ren Physiol Biochem 14:92–102
Murray BM, Brown GP, Schoenl M (1998) Interaction of gender and dietary protein on renal growth and the renal growth hormone-insulin-like growth factor axis. J Lab Clin Med 131:360–369
Mulroney SE, Woda C, Johnson M, Pesce C (1999) Gender differences in renal growth and function after uninephrectomy in adult rats. Kidney Int 56:944–953
Attia DM, Goldschmeding R, Attia MA, Boer P, Koomans HA, Joles JA (2003) Male gender increases sensitivity to renal injury in response to cholesterol loading. Am J Physiol Renal Physiol 284:F718–F726
Acknowledgements
We are grateful to the participating families and to the staff of the Obstetric Departments of the University Hospital of Copenhagen for excellent cooperation. We appreciate the skilled help of our assisting nurses and students, and we thank Kim Fleischer Michaelsen and the staff at the Human Milk Bank at Hvidovre Hospital, for generously letting us use their laboratory facilities. The present study was supported by: the Danish Research Council (no. 9700833), Research Foundation of The Copenhagen Hospital Corporation (no. 109/00 and 134), the European Commission (no. QLK4–1999–01422 and QLRT-2001–00269), and the Ville Heise Foundation.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Schmidt, I.M., Damgaard, I.N., Boisen, K.A. et al. Increased kidney growth in formula-fed versus breast-fed healthy infants. Pediatr Nephrol 19, 1137–1144 (2004). https://doi.org/10.1007/s00467-004-1567-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-004-1567-0