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Editor—Matos et al 1 have used indirect measurements in their recent paper to conclude that the urinary excretion of solutes cannot be evaluated by factoring them against urinary creatinine in the first week of life. They say they “would have preferred to compare the reported spot urine results with normal data obtained by complete, timed urine collection” because this would have given them “the ultimate proof of [their] assertion”, but seem unaware that such data already exist and that they contradict their conclusions.2-4
In the 1980s, we independently quantified creatinine excretion in 101 infants of 26–42 weeks gestation (and 640 to 4200 g birth weight) when 1.5–63 days old. In Newcastle, we used a constant inulin infusion technique5 to measure urine flow in 41 babies, some of whom required ventilatory support.3 In London, 24 hour urine collections were obtained from 60 stable babies using a continuously drained adhesive urine bag.4 Our measurements of daily urinary creatinine excretion were virtually identical. In Newcastle, we reported mean values of 104 μmol/kg in the first week of life and 95 μmol/kg in weeks 2 to 4, and in London we recorded an arithmetic mean of 96 μmol/kg throughout. In each case, the values were unaffected by gestational or postnatal age, or by the baby's weight centile.
Because urinary creatinine excretion per kilogram is constant from two days to two months, it follows that ratios of the concentrations of substances to creatinine can be used to estimate urinary excretion during that time. Similarly, urine flow can be estimated from the reciprocal of the creatinine concentration. Indeed, the coefficient of determination (r 2) of the measured sodium excretion rate was 0.94 when correlated with the urinary sodium to creatinine ratio, compared with 0.14 when correlated with the urinary sodium concentration alone.3 In other words, whereas the raw sodium concentration only predicted 14% of the differences in sodium excretion rates, the sodium to creatinine ratio predicted 94% of the variation seen. Although such estimates are inevitably imprecise (the sodium excretion and urine flow estimates each having 95% confidence intervals of 62 to 161%), they are better than estimates based on a knowledge of urinary sodium concentration or osmolality alone, as suggested by Matos et al.1
Matos et al 1 concluded that urinary creatinine excretion was very variable because their urinary creatinine concentrations and urinary sodium to creatinine ratios varied widely, but this deduction does not necessarily follow. We present longitudinal data on 16 babies (mean of five data points each) obtained during the first week of life at the time of our earlier study,3 but not previously published, which undermine this conclusion. Creatinine excretion was very stable from day to day (despite some slight suggestion of a downward trend) particularly in individual babies, although urine flow and osmolar excretion varied widely. Creatinine excretion varied threefold, urine flow varied ninefold, and osmolar excretion tenfold (fig 1).
Serial daily urine excretion rates of creatinine, water (volume), and osmoles in 16 babies studied using inulin infusion during the first week of life.
We would contend that it is possible to obtain a clinically useful estimate of the excretion of a substance, x, in units/kg per day from an untimed (“spot”) urine sample using the simplified, but easily memorable, formula 0.1Ux/Uc, while urine volume in ml/kg per day can be approximated from 100/Uc, where Ux is the urine concentration of any substance in units/l, and Uc is the creatinine concentration in mmol/l. Such estimates, although imprecise, are of practical value in babies of any age.
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Dr Guignard and Dr Drukker respond:
Dr Coulthard and colleagues start their letter saying that we have used indirect measurements . . . to conclude that “the urinary excretion of solutes cannot be evaluated by factoring them against urinary creatinine in the first week of life”. This is clearly not the case. We drew our conclusion from simple direct (!!) measurement of the urinary creatinine concentration and osmolality in fresh spot urine samples. Therefore the data are what they are: the urinary creatinine concentrations show a wide scatter that is somewhat corrected but not explained by different states of urine concentration, as shown when the data were factored by urine osmolality. We did not quote the paper of Al-Dahhanet al 1-1 or that of Coulthardet al 1-2 precisely because they did not provide simple data such as the urinary creatinine concentration in spot urine samples. Actually, the same wide dispersion of urinary creatinine excretion rates can be found in the paper by Al-Dahhan et al.1-1 During the first 10 days of life, we see (figs 5 and 6) that 24 hour creatinine excretion rates vary from about 40 to 450 μmol/l per day. The variation is still substantial (30–180 μmol/l per day) when the excretion rate is expressed per kg body weight. The findings by Al-Dahhan et al therefore support our contention, rather than that they disagree with our results.1-3
Why there is such a scatter in the urinary creatinine excretion rates is not really known and was not addressed in our paper nor by Al-Dahhan et al. It certainly is a rather amazing finding, taking into account that newborn babies have about the same birth weight, receive similar nutrition, and have the same kind of bodily activity. This finding probably reflects, at least in part, the special situation of the neonate, who has to cope with the significant creatinine load transmitted from the mother, at a time when its glomerular filtration rate is very low and there is net creatinine reabsorption by the renal tubules which are presumably leaky.1-4
Some of the data of Coulthard et al 1-2 also confirm our recent work. We refer to their observation that the clearance of creatinine underestimates inulin clearance. This supports our thesis that the neonatal tubule reabsorbs creatinine.1-4 The other findings by Coulthardet al are more difficult to interpret. The daily excretion of creatinine indeed shows less variation (50–150 μmol/kg per day) than found by Al-Dahhan et al 1-1 and us.1-3 One has, however, to take into account that these data were actually calculated without urine collection! Their data are indeed indirect measurements, not ours! Instead of collecting urine, the authors extrapolated urine flow rates from inulin concentrations in spot urine samples taken in the course of a constant (± 24 hours) infusion of inulin. It is clear that such values cannot provide reference data on absolute rates of urinary excretion of solutes! Precisely because of this significant drawback, we also do not find much use for the proposed formula 0.1Ux/Uc. For this formula, the urine flow rate (ml/kg per day) has to be “approximated” by another formula (100/Uc), again drawn from studies without urine collections. Estimating such values appears to us a little risky, even if the formula is “easily memorable”.