long-term follow-up of extremely low birth weight infants

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Pediatr Nephrol (2006) 21:299 DOI 10.1007/s00467-005-2062-y LETTER TO THE EDITORS Caroline Jones · Brian Judd Long-term follow-up of extremely low birth weight infants Received: 27 June 2005 / Accepted: 15 July 2005 / Published online: 27 October 2005 # IPNA 2005 Sirs, Drs. Juan Rodriguez-Soriano et al reported the clinical and functional renal parameters in 40 children born weighing less than 1000 g at birth now aged between 6.1 and 12.4 years [1]. The authors demonstrated a reduction in tubular function compared to 43 controls. TmP/GFR and TRP were signif- icantly lower than in controls and urinary calcium excretion was higher. The authors postulated that the defect in renal tubular reabsorption of phosphate was secondary to the use of nephrotoxic antibiotics during the neonatal period. In a previous study we also observed that urinary cal- cium excretion was higher in 46 children born less than 32 weeks gestation compared to 40 term controls at age 7– 9 years [2]. Twenty-seven children in the preterm group were classified as having hypercalciuria. There were no significant differences in neonatal covariables between children considered to have hypercalciuria and normo- calciuria. The neonatal covariables examined included gestational age, birth weight, number of days requiring oxygen, days on total parenteral nutrition and maximum serum creatinine. Children considered to have hypercal- ciuria were more likely to have been at risk of gentamicin- induced nephrotoxicity (p=0.027). This association was referred to in the paper by Drs. Juan Rodriguez-Soriano et al [1]. In the same study we also observed a significant neg- ative relationship between the number of days of pre- scribed gentamicin and minimum serum phosphate that was recorded in the neonatal period (r=ř0.41, p=0.012). In 23 out of 27 ex-preterm children considered to have hy- percalciuria, tubular phosphate reabsorption was measured using the formula [3]: Tp=GFR ¼ Sp Up Scr Ucr where Scr is serum creatinine (mmol/l), UCr is urine creatinine (mmol/l), Up is urine phosphate (mmol/l) and Sp is serum phosphate (mmol/l). For the purpose of our study, ethical approval was not given to perform venepuncture in ex-preterm children who were considered to have normocalciuria or in the 40 term controls. The median Tp/GFR was 3.9 mg/dl with a range of 2.5–4.9. The published mean value for this age group is 4.4€0.6 [3]. The median calculated SD score for Tp/GFR was ř0.87 (range 3.3–0.9). The median TpGFR in children who had a recorded high gentamicin level was 3.7 (range 2.4–4.6) and was lower than that recorded in children that had hypercalciuria but were not considered to be at risk of aminoglycoside nephrotoxicity (median 4.2, range 3.0–4.9 mg/dl). This difference was however not significant, but may reflect the small number of children investigated. Independently we have postulated a similar hypothesis to Juan Rodriguez-Soreno et al, that in ex-preterm children the reduction in tubular phosphate reabsorption and increase in urinary calcium excretion may be secondary to aminoglycoside nephrotoxicity. It is possible that the association of hypercalciuria with increased aminoglycoside levels is an epiphenomenon, as it is difficult to separate the influence of haemodynamic stability, other drugs, anoxia and from the independent effects of aminoglycosides. However, in view of these findings, future studies may identify whether the use of aminoglycosides in the neonatal period results in long- term renal dysfunction and has any long-term sequelae. References 1. Rodriguez-Soriano J, Aguirre M, Oliveros R, Vallo A (2005) Long-term renal follow-up of extremely low birth weight in- fants. Pediatr Nephrol 20:579–584 2. Jones CA, Bowden LS, Watling R, Ryan SW, Judd BA (2001) Hypercalciuria in ex-preterm children aged 7–8 years. Pediatr Nephrol 16:665–671 3. Stark H, Eisenstein B, Teider M, Rachmel A, Alpert G (1986). Direct measurement of Tp/GFR: A simple and reliable pa- rameter of renal phosphate handling. Nephron 44:125–128 C. Jones ( ) ) · B. Judd Department of Nephrology, Royal Liverpool Children’s Hospital NHS Trust, Eaton Road, Liverpool, L12 2AP, UK e-mail: [email protected] Tel.: +44-151-2525221 Fax: +44-151-2525928

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Page 1: Long-term follow-up of extremely low birth weight infants

Pediatr Nephrol (2006) 21:299DOI 10.1007/s00467-005-2062-y

L E T T E R T O T H E E D I T O R S

Caroline Jones · Brian Judd

Long-term follow-up of extremely low birth weight infants

Received: 27 June 2005 / Accepted: 15 July 2005 / Published online: 27 October 2005� IPNA 2005

Sirs,Drs. Juan Rodriguez-Soriano et al reported the clinical andfunctional renal parameters in 40 children born weighingless than 1000 g at birth now aged between 6.1 and12.4 years [1].

The authors demonstrated a reduction in tubular functioncompared to 43 controls. TmP/GFR and TRP were signif-icantly lower than in controls and urinary calcium excretionwas higher. The authors postulated that the defect in renaltubular reabsorption of phosphate was secondary to the useof nephrotoxic antibiotics during the neonatal period.

In a previous study we also observed that urinary cal-cium excretion was higher in 46 children born less than32 weeks gestation compared to 40 term controls at age 7–9 years [2]. Twenty-seven children in the preterm groupwere classified as having hypercalciuria. There were nosignificant differences in neonatal covariables betweenchildren considered to have hypercalciuria and normo-calciuria. The neonatal covariables examined includedgestational age, birth weight, number of days requiringoxygen, days on total parenteral nutrition and maximumserum creatinine. Children considered to have hypercal-ciuria were more likely to have been at risk of gentamicin-induced nephrotoxicity (p=0.027). This association wasreferred to in the paper by Drs. Juan Rodriguez-Soriano etal [1].

In the same study we also observed a significant neg-ative relationship between the number of days of pre-scribed gentamicin and minimum serum phosphate thatwas recorded in the neonatal period (r=�0.41, p=0.012). In23 out of 27 ex-preterm children considered to have hy-percalciuria, tubular phosphate reabsorption was measuredusing the formula [3]:

Tp=GFR ¼ Sp� Up� Scr

Ucr

where Scr is serum creatinine (mmol/l), UCr is urinecreatinine (mmol/l), Up is urine phosphate (mmol/l) andSp is serum phosphate (mmol/l).

For the purpose of our study, ethical approval was notgiven to perform venepuncture in ex-preterm childrenwho were considered to have normocalciuria or in the40 term controls. The median Tp/GFR was 3.9 mg/dl witha range of 2.5–4.9. The published mean value for this agegroup is 4.4€0.6 [3]. The median calculated SD score forTp/GFR was �0.87 (range 3.3–0.9). The median TpGFRin children who had a recorded high gentamicin level was3.7 (range 2.4–4.6) and was lower than that recorded inchildren that had hypercalciuria but were not consideredto be at risk of aminoglycoside nephrotoxicity (median4.2, range 3.0–4.9 mg/dl). This difference was howevernot significant, but may reflect the small number ofchildren investigated. Independently we have postulated asimilar hypothesis to Juan Rodriguez-Soreno et al, that inex-preterm children the reduction in tubular phosphatereabsorption and increase in urinary calcium excretionmay be secondary to aminoglycoside nephrotoxicity.

It is possible that the association of hypercalciuria withincreased aminoglycoside levels is an epiphenomenon, asit is difficult to separate the influence of haemodynamicstability, other drugs, anoxia and from the independenteffects of aminoglycosides. However, in view of thesefindings, future studies may identify whether the use ofaminoglycosides in the neonatal period results in long-term renal dysfunction and has any long-term sequelae.

References

1. Rodriguez-Soriano J, Aguirre M, Oliveros R, Vallo A (2005)Long-term renal follow-up of extremely low birth weight in-fants. Pediatr Nephrol 20:579–584

2. Jones CA, Bowden LS, Watling R, Ryan SW, Judd BA (2001)Hypercalciuria in ex-preterm children aged 7–8 years. PediatrNephrol 16:665–671

3. Stark H, Eisenstein B, Teider M, Rachmel A, Alpert G (1986).Direct measurement of Tp/GFR: A simple and reliable pa-rameter of renal phosphate handling. Nephron 44:125–128

C. Jones ()) · B. JuddDepartment of Nephrology,Royal Liverpool Children’s Hospital NHS Trust,Eaton Road, Liverpool, L12 2AP, UKe-mail: [email protected].: +44-151-2525221Fax: +44-151-2525928