Abstract
Premature infants undergo intensive growth during the postnatal period. Adequate mineralization is dependent on sufficient intake of calcium (Ca) and phosphorus (P). However, Ca and P supplementation can be associated with some risks, for example development of nephrocalcinosis. We investigated pathophysiological risk factors in premature very low birth weight (VLBW) infants associated with the development of nephrocalcinosis. From June 1994 to September 1995 all preterm neonates with a birth weight below 1,500 g were screened prospectively. At regular intervals of 2 weeks, ultrasonography (US) of the kidneys was performed and parameters of mineral metabolism were assessed in blood and spot urine samples. For analysis, premature infants with nephrocalcinosis (group N) were compared with infants without nephrocalcinosis (group R) and with a retrospectively pair-matched subgroup of premature infants without nephrocalcinosis (control group C) taken from the same study. Nephrocalcinosis was detected in 20 of 114 preterm neonates (group N, 17.5%). Of these 20 infants with nephrocalcinosis, 16 presented with a tendency towards systemic acidosis (pH<7.25) on day 2–7, compared with only 4 of 20 premature infants of the control group. Premature infants of group N had a lower serum P at 2 weeks of life and 5 (versus 0 patients of the control group C) had transient hypophosphatemia (serum P<1.6 mmol/l). Moreover, the Ca/creatinine ratio in spot urine specimens tended to be higher (P<0.1) in patients developing nephrocalcinosis. There were no significant differences in the duration of ventilation, the length of stay in the intensive care unit, and duration and frequency of furosemide and steroid treatment between the groups N and C. VLBW premature infants developing nephrocalcinosis frequently presented with slightly impaired acid-base homoeostasis within the 1st week, followed by signs of impaired mineralization (and immature or impaired renal function) within 2 weeks. In VLBW premature infants, close observation of acid-base status and regular analysis of spot urine specimens (Ca, P, creatinine) during the first weeks of life may help to identify those premature infants at risk for nephrocalcinosis.
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References
Atkinson SA (1994) Calcium and phosphorus needs of premature infants. Nutrition 10:66–68
Pohlandt F (1994) Prevention of postnatal bone demineralization in very low-birth-weight infants by individually monitored supplementation with calcium and phosphorus. Pediatr Res 35:125–129
Trotter A, Pohlandt F (2002) Calcium and phosphorus retention in extremely preterm infants supplemented individually. Acta Paediatr 91:680–683
Lorenz JM, Kleinman LI, Ahmed G, Markarian K (1995) Phases of fluid and electrolyte homeostasis in the extremely low birth weight infant. Pediatrics 96:484–489
Sonntag J, Prankel B, Waltz S (1996) Serum creatinine concentration, urinary creatinine excretion and creatinine clearance during the first 9 weeks in preterm infants with a birth weight below 1500 g. Eur J Pediatr 155:815–819
Kreuder J, Otten A, Reiter HL, Klingmüller V, Wolf H (1990) Efficiency and complications of calcium and phosphorus supplementation in very low birth weight infants. Monatsschr Kinderheilkd 138:775–779
Pfitzer A, Nelle M, Rohrschneider W, Linderkamp O, Tröger J (1998) Incidence of ultrasound findings indicative of nephrocalcinosis in low birth weight infants. Z Geburtsh Neonatol 202:158–163
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
Jacinto JS, Modanlou HD, Crade M, Strauss AA, Bosu SK (1988) Renal calcification incidence in very low birth weight infants. Pediatrics 81:31–35
Saarela T, Vaarela A, Lanning P, Koivisto M (1999) Incidence, ultrasonic patterns and resolution of nephrocalcinosis in very low birthweight infants. Acta Paediatr 88:655–660
Short A, Cooke RW (1991) The incidence of renal calcifications in preterm infants Arch Dis Child 66:412–417
Narendra A, White MP, Rolton HA, Alloub ZI, Wilkinson G, McColl JH, Beattie J (2001) Nephrocalcinosis in preterm babies. Arch Dis Child Fetal Neonatal Ed 85:F207–F213
Adams ND, Rowe JC (1992) Nephrocalcinosis. Clin Perinatol 19:179–195
Hufnagle KG, Khan SN, Penn D, Cacciarelli A, Williams P (1982) Renal calcifications: a complication of long term furosemide therapy in preterm infants. Pediatrics 70:360–363
Bererd E, Dageville C, Bekri S, Boutte P, Coussement A, Mariani R (1995) Nephrocalcinosis and prematurity: importance of urate and oxalate excretion. Nephron 69:237–241
Campfield T, Braden G, Flynn-Valone P, Powell S (1997) Effect of diuretics on urinary oxalate, calcium, and sodium excretion in very low birth weight infants. Pediatrics 99:814–818
Hoppe B, Hesse A, Neuhaus T, Fanconi S, Forster I, Blau N, Leumann E (1993) Urinary saturation and nephrocalcinosis in preterm infants: effect of parenteral nutrition. Arch Dis Child 69:299–303
Schell-Feith EA, Kist-Van Holthe JE, Conneman N, Van Zwieten PH, Holscher HC, Zonderland HM, Brand R, Van der Heijden BJ (2000) Etiology of nephrocalcinosis in preterm neonates: association of nutritional intake and urinary parameters. Kidney Int 58:2102–2110
Giapros VI, Papaloukas AL, Challa AS, Nikolopoulos PD, Tsampoulas CG, Andronikou SK (2003) Urinary lithogenic and inhibitory factors in preterm neonates receiving either total parenteral nutrition or milk formula. Eur J Pediatr 162:481–487
Campfield T, Bednarek FJ, Pappagallo M, Hampf F, Ziewacz J, Wellmann J, Rockwell G, Braden G, Flynn-Valone P, Neylan M, Pangan A (1999) Nephrocalcinosis in premature infants: variability in ultrasound detection. J Perinatol 19:498–500
Pohlandt F, Müller M (1987) Renal echogenicity in VLBW infants supplemented with Ca and P to prevent bone demineralization. Pediatr Res 22:233
Gökce C, Gökce Ö, Baydine C (1991) Use of random urine samples to estimate total urinary calcium and phosphate excretion. Arch Intern Med 151:1587–1588
Kalhoff H (2003) Osteomalazie-(Rachitis-)Prophylaxe bei Frühgeborenen. In: Bassler D, Forster J, Antes G (eds) Evidenzbasierte Pädiatrie. Thieme, Stuttgart, pp 1–17
Schönau E, Kalhoff H, Rauch F, Manz F (2001) Knochenentwicklung bei Frühgeborenen: Physiologie und Ernährung. In: Wollmann HA, Ranke MB (eds) Perinatale Endokrinologie. Palatium Verlag, Mannheim, pp 159–170
Schell-Feith EA, Holscher HC, Zonderland HM, Kist-Van Holthe JE, Conneman N, Van Zwieten PHT, Brand R, Van der Heijen AJ (2000) Ultrasonic features of nephrocalcinosis in preterm neonates. Br J Radiol 73:1185–1191
Pope JC, Trusler LA, Klein AM, Walsh, WF, Yared A, Brock JW (1996) The natural history of nephrocalcinosis in premature infants treated with loop diuretics. J Urol 156:709–712
Ezzedeen F, Adelman RD, Ahlfors CE (1988) Renal calcification in preterm infants: pathophysiology and long-term sequelae. J Pediatr 113:532–539
Hellstern G, Pöschl J, Linderkamp O (2003) Renal phosphate handling of premature infants of 23–25 weeks gestational age. Pediatr Nephrol 18:756–758
Yanagawa N, Lee DBN (1992) Renal handling of calcium and phosphorus. In: Coe FL, Favus MJ (eds) Disorders of bone and mineral metabolism. Raven Press, New York, pp 3–40
Green J, Kleeman CR (1991) Role of bone in regulation of systemic acid-base balance. Kidney Int 39:9–26
Krieger NS, Sessler NE, Bushinsky DA (1992) Acidosis inhibits osteoblastic and stimulates osteoclastic activity in vitro. Am J Physiol 262:F442–F448
Kalhoff H, Diekmann L, Rudloff S, Manz F (2001) Renal excretion of calcium and phosphorus in premature infants with incipient late metabolic acidosis. J Pediatr Gastroent Nutr 33:565–569
Tsukahara H, Fujii Y, Tsuchida S, Hiraoka M, Morikawa K, Haruki S, Sudo M (1994) Renal handling of albumin and beta-2-microglobulin in neonates. Nephron 68:212–216
Streitman K, Toth A, Horvath I, Talosi G (2001) Renal injury in perinatal hypoxia: ultrasonography and changes in renal function. Eur J Pediatr 160:473–477
Saarela T, Lanning P, Koivisto M (1999) Prematurity-associated nephrocalcinosis and kidney function in early childhood. Pediatr Nephrol 13:886–890
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Hein, G., Richter, D., Manz, F. et al. Development of nephrocalcinosis in very low birth weight infants. Pediatr Nephrol 19, 616–620 (2004). https://doi.org/10.1007/s00467-004-1428-x
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DOI: https://doi.org/10.1007/s00467-004-1428-x