muscle mass that is 24% of body weight, and
growth in infancy is not associated with a major
change in the proportion of muscle mass.
25
During childhood, accretion of muscle mass
exceeds the increase in body weight so that by
11 to 13 years, 39% of body weight is muscle,
approaching the value of 43% in male adults.
GFR measurement, by
51
Cr-EDTA clear-
ance, has been shown to reach adult values of
114 ml/min/1.73 m
2
by 18 months, and then to
be constant up to 17 years.
26
This makes the
measurement of serum creatinine unreliable
when its concentration rises continuously
because of an increase in muscle mass. The
cystatin C values in our study (fig 1A) mirror
the reported GFR, falling to within the adult
range by 1 year. Cystatin C is raised preterm
until birth; the maternal contribution of cysta-
tin C is unknown.
It has been shown that GFR increases with
postconceptional age at a rate that accelerates
with maturation.
15 16 27
From 20 weeks of gesta-
tion, kidney weight and body weight have a lin-
ear relation to gestational age and body surface
area.
28
Although there are studies that have
measured the changes of GFR occurring in the
last weeks of gestation the results are not
uniform. A study by Aperia et al,
29
measuring
creatinine clearance, showed that preterm
infants, born before 34 weeks’ gestation, had
significantly lower GFRs than full term infants,
and that this diVerence persisted for up to 3–5
weeks postnatally. During the 1st week of life,
the GFR increased significantly more in full
term than preterm infants. Between 1 and 5
weeks of age the GFR increased at a slower rate
in both sets of infants. Brion and colleagues
30
have also shown that GFR measurement, using
inulin and creatinine clearance, increases with
gestational and postnatal age, whether ex-
pressed as absolute value (for each unit surface
area) or for each kg body weight.
Creatinine concentrations were significantly
diVerent between the premature and term
infants. This could be because of the diVerent
postnatal sampling points: the term samples
were collected at day 2 versus day 1 for the
premature infants.
19
Although there are indica-
tions that creatinine reabsorption is increased
in the preterm kidney,
31
this is likely to be pas-
sive diVusion down a concentration gradient, a
process unlikely to occur with a protein like
cystatin C. Once filtered, cystatin C would
normally be reabsorbed and degraded by the
proximal tubular epithelial cells. In the ne-
onate, the tubular length is less than in the
adult so the proportion reabsorbed is likely to
be much less, but the protein will still be
removed and pass into the urine. The much
smaller and statistically insignificant diVer-
ences between the premature and term cystatin
C concentrations suggests a smaller maternal
contribution to the neonatal circulatory pool.
Although a longer half life of cystatin C in the
circulation might contribute to the sustained
level at day 7 in the term infants, our own
(unpublished, 1995) studies during adult
donor nephrectomies suggest that it is, in fact,
not significantly diVerent to that of creatinine.
There is evidence indicating that the longer
half life of dextrans might be the result of
diVerences in the permeability of the neonatal
glomerulus
32
; however, it is possible that this
could be explained by the reduced GFR that is
also present, rather than permeability diVer-
ences. In previous work, looking at the
glomerular permeability and tubular reabsorp-
tion of proteins in neonates, it was concluded
that there was insuYcient evidence to establish
whether the increase in albumin excretion was
the result of an increase in permeability or a
decrease in tubular reabsorption.
33
However,
our data and that of others suggest that a pro-
tein with the molecular weight of cystatin C is
unlikely to be retained to any great degree by
the neonatal kidney. Whereas in the adult kid-
ney, the passage of cystatin C through the
glomerular barrier is less free than the much
smaller creatinine molecule, it will be closer to
that of creatinine in the neonate because of the
greater overall permeability of the neonatal
barrier.
In summary, we have shown that cystatin C
is a better marker of GFR than creatinine in the
paediatric population because it appears to
mirror what is known about the maturation of
renal function more closely. In premature
infants, cystatin C is significantly raised at all
gestational ages. Cystatin C concentrations in
children reach adult values by the age of 1 year
(range, 0.50–1.27 mg/litre; adult range, 0.51–
0.98); therefore, a separate reference range is
not required. Below the age of 1 year, cystatin
C values are higher, reflecting the immaturity
of the kidneys (< 1 year, 0.59–1.97 mg/litre).
Creatinine does not show these trends and is
influenced mainly by the increase in muscle
mass during growth. At birth, the kidneys are
immature and cystatin C concentration
changes suggest it takes 12 months to attain
maturity (in accord with reference GFR meas-
urements), whereas serum creatinine concen-
trations are influenced by increasing muscle
mass and do not reach adult values until after
puberty. Cystatin C concentrations are eVec-
tively constant from 1 year of age upwards.
This suggests that cystatin C might oVer a
considerable advantage to paediatric nephrolo-
gists in the measurement of GFR.
HF was supported by a grant from Dade Behring Marburg
GmbH, Marburg, Germany. We are grateful to colleagues at the
Birmingham Children’s Hospital for collection of some of the
paediatric samples.
1 Chantler C. The measurement of renal function in children:
a review. Guy’s Hospital Reports 1973;122:25–41.
Key messages
+ Cystatin C is a better marker than creati-
nine of glomerular filtration rate (GFR)
in preterm infants
+ A single reference range for plasma
cystatin C can be used, regardless of sex,
from 1 year of age
+ Cystatin C oVers a more specific and
practical measure for monitoring GFR in
the paediatric population than does
creatinine
74 Finney, Newman, Thakkar, Fell, Price