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=0.41, 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]:
Up  Scr
Tp=GFR ¼ Sp

Ucr
C. Jones ()) · B. Judd
Department of Nephrology,
Royal Liverpool Children’s Hospital NHS Trust,
Eaton Road, Liverpool, L12 2AP, UK
e-mail: caroline.jones@rlc.nhs.uk
Tel.: +44-151-2525221
Fax: +44-151-2525928
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 0.87 (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