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Urinary excretion of calcium and phosphate in preterm infants

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Abstract

The aims of this study were to determine reference ranges for the urinary calcium (UCa/Cr) and phosphate (UPO4/Cr) creatinine ratios and to study factors influencing these ratios in a representative population of preterm infants managed according to current nutritional guidelines. Spot urine samples were obtained from 186 preterm infants (gestation 24–34 weeks) for measurement of UCa/Cr and UPO4/Cr ratios as part of a routine metabolic bone screening program, once every 2–4 weeks from the 3rd to the 18th week of life. Data were also collected on gender, appropriate or small for gestational age (SGA), nutrition [total parenteral nutrition (TPN), preterm or term formula, and breast milk], plasma Ca, PO4, urea, and electrolytes and on the use of drugs (frusemide, dexamethasone, and theophylline). Data from infants treated with any of these three drugs were analysed separately and not included in establishing the reference ranges for UCa/Cr and UPO4/Cr. The mean gestational age of the study population was 28 weeks (range 24–34 weeks). The 95th percentile for UCa/Cr at 3 weeks of age was 3.8 mmol/mmol and decreased significantly with increasing postnatal age ( P <0.001). The 95th percentile for UPO4/Cr was 26.69 mmol/mmol at 3 weeks of age, but this did not change significantly with increasing postnatal age ( P =0.296). On univariate analysis there was no significant association of UCa/Cr and UPO4/Cr with gender and type of enteral nutrition. The UCa/Cr was lower in infants who were SGA ( P =0.013) and with low plasma Ca ( P =0.008). Infants on TPN had significantly higher UCa/Cr ( P =0.019) and lower UPO4/Cr ratios ( P ≤0.001). Multivariate analysis confirmed the decrease in UCa/Cr ratio with increasing postnatal age, but the SGA effect was eliminated. The use of furosemide ( P <0.001) and theophylline ( P =0.003) was associated with a significant increase in the UCa/Cr ratio. The use of dexamethasone was also associated with an increase in UCa/Cr ratio, but this did not achieve statistical significance ( P =0.339). The use of furosemide, theophylline, and dexamethasone had no effect on UPO4/Cr. We report a reference range for UCa/Cr and UPO4/Cr ratios and factors influencing these ratios in a representative population of preterm infants between 24 and 34 weeks gestation, managed according to current nutritional guidelines.

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References

  1. Ghazali S, Barratt TM (1974) Urinary excretion of calcium and magnesium in children. Arch Dis Child 49:97–101

    CAS  PubMed  Google Scholar 

  2. Sargent JD, Stukel TA, Kresel J, Klein RZ (1993) Normal values for random urinary calcium to creatinine ratios in infancy. J Pediatr 123:393–397

    CAS  PubMed  Google Scholar 

  3. Reusz SS, Dobos M, Byrd D, Sallay P, Miltenyi M, Tulassay T (1995) Urinary calcium and oxalate excretion in children. Pediatr Nephrol 9:39–44

    CAS  PubMed  Google Scholar 

  4. Matos V, Malle GV, Boulat OO, Markert M, Bachmann C, Guignard JP (1997) Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios in a healthy pediatric population. J Pediatr 131:252–257

    CAS  PubMed  Google Scholar 

  5. Vachvanichsanong P, Lebl L, Moore ES (2000) Urinary calcium excretion in healthy Thai children. Pediatr Nephrol 14:847–850

    Article  CAS  PubMed  Google Scholar 

  6. Schell-Feith EA, Kist-van Holthe JE, Conneman N, Zwieten PH van, Holscher HC, Zonderland HM, Brand R, Heijden BJ van der (2000) Etiology of nephrocalcinosis in preterm neonates: association of nutritional intake and urinary parameters. Kidney Int 58:2102–2110

    CAS  PubMed  Google Scholar 

  7. Karlen J, Aperia A, Zetterstrom R (1985) Renal excretion of calcium and phosphate in preterm and term infants. J Pediatr 106:814–819

    CAS  PubMed  Google Scholar 

  8. Rowe J, Rowe D, Horak E, Spackman T, Saltzman R, Robinson S, Philipps A, Raye J (1984) Hypophosphatemia and hypercalciuria in small premature infants fed human milk: evidence for inadequate dietary phosphorus. J Pediatr 104:112–117

    CAS  PubMed  Google Scholar 

  9. Lyon AJ, McIntosh N (1984) Calcium and phosphorus balance in extremely low birth weight infants in the first 6 weeks of life. Arch Dis Child 59:1145–1150

    CAS  PubMed  Google Scholar 

  10. Short A, Cooke RWI (1991) The incidence of renal calcification in preterm infants. Arch Dis Child 66:412–417

    CAS  PubMed  Google Scholar 

  11. Short A, Shaw NJ, Weindling AM (1990) Nephrocalcinosis and phosphate supplementation in a preterm infant. Acta Paediatr Scand 79:968–969

    CAS  PubMed  Google Scholar 

  12. Saarela T, Vaarala A, Lanning P, Koivisto M (1999) Incidence, ultrasonic patterns and resolution of nephrocalcinosis in very low birth weight infants. Acta Paediatr 88:655–660

    Article  CAS  PubMed  Google Scholar 

  13. Narendra A, White MP, Rolton HA, Alloub ZI, Wilkinson G, McColl JH, Beattie J (2001) Nephrocalcinosis in preterm babies. Arch Dis Child 85:207–213

    Article  Google Scholar 

  14. Jacinto JS, Modanlou HD, Crade M, Strauss AA, Bosu SK (1988) Renal calcification in very low birth weight infants. Pediatrics 81:31–35

    CAS  PubMed  Google Scholar 

  15. Hoppe B, Duran I, Martin A, Kribs A, Benz-Bohm G, Michalk DV, Roth B (2002) Nephrocalcinosis in preterm infants: a single center experience. Pediatr Nephrol 17:264–268

    Article  PubMed  Google Scholar 

  16. Atkinson SA, Shah JK, McGee C, Steele BT (1988) Mineral excretion in premature infants receiving various diuretic therapies. J Pediatr 113:540–545

    CAS  PubMed  Google Scholar 

  17. Vileisis RA (1990) Furosemide effect on mineral status of parenterally nourished premature neonates with chronic lung disease. Pediatrics 85:316–322

    CAS  PubMed  Google Scholar 

  18. Zanardo V, Dani C, Trevisanuto D, Meneghetti S, Guglielmi A, Zacchello G, Cantarutti F (1995) Methylxanthines increase renal calcium excretion in preterm infants. Biol Neonate 68:169–174

    CAS  PubMed  Google Scholar 

  19. Mazkereth R, Laufer J, Jordan S, Pomerance JJ, Boichis H, Reichman B (1997) Effects of theophylline on renal functions in premature infants. Am J Perinatol 14:45–49

    CAS  PubMed  Google Scholar 

  20. Kamitsuka MD, Williams MA, Nyberg DA, Fox KA, Lee DL, Hickok D (1995) Renal calcification: a complication of dexamethasone therapy in preterm infants with bronchopulmonary dysplasia. J Perinatol 15:359–363

    CAS  PubMed  Google Scholar 

  21. Nordin BEC (1959) Assessment of calcium excretion from the urinary calcium/creatinine ratio. Lancet I:368–371

    Article  Google Scholar 

  22. Knapp EL (1947) Factors influencing the urinary excretion of calcium. 1. In normal persons. J Clin Invest 26:182–202

    CAS  Google Scholar 

  23. Esbjorner E, Jones IL (1995) Urinary calcium excretion in Swedish children. Acta Paediatr 84:156–159

    CAS  PubMed  Google Scholar 

  24. Hillman LS, Johnson LS, Lee DZ, Vieira NE, Yergey AL (1993) Measurement of true absorption, endogenous fecal excretion, urinary excretion, and retention of calcium in term infants by using a dual-tracer, stable-isotope method. J Pediatr 123:445–456

    Google Scholar 

  25. Abrams SA, Schanler RJ, Yergey AL, Vieira NE, Bronner F (1994) Compartmental analysis of calcium metabolism in very-low-birth-weight infants. Pediatr Res 36:424–428

    CAS  PubMed  Google Scholar 

  26. Hillman LS, Salmons SS, Erickson MM, Hansen JW, Hillman RE, Chesney R (1994) Calciurea and aminoaciduria in very low birth weight infants fed a high-mineral premature formula with varying levels of protein. J Pediatr 125:288–294

    CAS  PubMed  Google Scholar 

  27. Sulyok E, Varga F, Gyory E, Jobst K, Csaba IF (1980) On the mechanism of renal sodium handling in new born infants. Biol Neonate 37:75–79

    CAS  PubMed  Google Scholar 

  28. Gillini F, Maggio L, Romagnoli C, Marrocco G, Tortorolo G (2000) Progression of renal function in preterm neonates with gestational age ≤32 weeks. Pediatr Nephrol 15:119–124

    Article  PubMed  Google Scholar 

  29. Adelman RD, Solhaug MJ (2000) Calcium. In: Behrman RE, Kliegman RM, Jenson HB (eds) Nelson text book of pediatrics. Saunders, Philadelphia, pp 200–201

  30. Al-dahhan J, Stimmler L, Chantler C, Haycock GB (1988) Urinary creatinine excretion in the newborn. Arch Dis Child 63:398–402

    CAS  PubMed  Google Scholar 

  31. Coulthard MG, Hey EN, Al-dahhan J, Haycock GB (2000) Evaluating urinary flow and solute excretion from urinary creatinine in the first week of life. Arch Dis Child 82:F257–F258

    Article  CAS  Google Scholar 

  32. Siegel SR, Hadeed A (1987) Renal handling of calcium in the early new born period. Kidney Int 31:1181–1185

    CAS  PubMed  Google Scholar 

  33. Hoppe B, Hesse A, Neuhaus T, Fanconi S, Blau N, Roth B, Leumann E (1997) Influence of nutrition on urinary oxalate and calcium in preterm and term infants. Pediatr Nephrol 11:687–690

    Article  CAS  PubMed  Google Scholar 

  34. Vileisis RA (1987) Effect of phosphorous intake in total parenteral nutrition infusates in premature neonates. J Pediatr 110:586–590

    CAS  PubMed  Google Scholar 

  35. Hoppe B, Hesse A, Neuhaus T, Fanconi S, Forster I, Blau N, Leumann E (1993) Urinary saturation and nephrocalcinosis in preterm infants: effect of parentaral nutrition. Arch Dis Child 69:299–303

    CAS  PubMed  Google Scholar 

  36. NJ Bishop (1999) Metabolic bone disease. In: Rennie JM, Roberton NRC (eds) Text book of neonatology, 3rd edn. Churchill Livingstone, Edinburgh, pp 1002–1008

  37. Backstrom MC, Kouri T, Kuusela AL, Sievanen H, Koivisto AM, Ikonen RS, Maki M (2000) Bone isoenzyme of serum alkaline phosphatase and serum inorganic phosphate in metabolic bone disease of prematurity. Acta Paediatr 89:867–873

    Article  CAS  PubMed  Google Scholar 

  38. So NP, Osorio AV, Simon SD, Alon US (2001) Normal urinary calcium/creatinine ratios in African-American and Caucasian children. Pediatr Nephrol 16:133–139

    Article  CAS  PubMed  Google Scholar 

  39. Wong GWK, Lam CWK, Kwok MY, Mak TWL (1998) Urinary calcium excretion in Chinese adolescents. J Paediatr Child Health 34:226–228

    Article  CAS  PubMed  Google Scholar 

  40. Mihatsch WA, Muche R, Pohlandt F (1996) The renal phosphate threshold decreases with increasing post menstrual age in very low birth infants. Pediatr Res 40:300–303

    CAS  PubMed  Google Scholar 

  41. McCrory WW, Forman CW, McNamara H, Barnett HL (1952) Renal excretion of inorganic phosphate in newborn infants. J Clin Invest 31:357–366

    CAS  PubMed  Google Scholar 

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Acknowledgement

We are grateful to Dr. B. Holland, Consultant Neonatalogist, The Queen Mother’s Hospital, Glasgow for allowing us to collect the clinical and biochemical data of the infants.

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Correspondence to Narendra Aladangady.

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Editorial comment: this paper describing urinary excretion of calcium and phosphate in preterm infants elicited completely different reactions from the three referees selected to review the manuscript. It is important to establish reference ranges for urinary excretion of these minerals. Nevertheless, it is also important to understand the effect of dietary intake of both calcium and phosphate in defining normative data. It is essential that readers of this article also read the accompanying commentary by Professor Frank Pohlandt.

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Aladangady, N., Coen, P.G., White, M.P. et al. Urinary excretion of calcium and phosphate in preterm infants. Pediatr Nephrol 19, 1225–1231 (2004). https://doi.org/10.1007/s00467-004-1574-1

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  • DOI: https://doi.org/10.1007/s00467-004-1574-1

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