Immunoreactive renin concentrations in healthy children from birth to adolescence1
Introduction
To determine the activation of the renin–angiotensin–aldosterone system, measurement of angiotensin II is the most accurate parameter [1]. However, this is a rather cumbersome procedure restricted to a small number of research laboratories [2]. Therefore, determination of plasma renin activity (PRA) has become the method of choice; reference values exist for all age groups 3, 4, 5, 6. Measurement of PRA is especially important in various renal and adrenal diseases, salt-losing disorders and in the differential diagnosis of hypertension 7, 8, 9, 10. PRA depends on two variables, the renin concentration and the concentration of angiotensinogen, as the latter is close to the Michaelis constant, Km, of the reaction under normal conditions 7, 11. In situations where the renin substrate concentration is either abnormally high or low, PRA, when used as a measure of the renin concentration, will over- or underestimate the true renin concentration 2, 7, 10, 11, 12, 13, 14, 15. PRA, when used as a measure of the plasma's capacity to produce angiotensin II, has also been shown to give falsely low values in samples from patients suffering from liver cirrhosis [15]. Moreover, methodological problems in assay performance and standardization (in vitro procedure, large inter-laboratory variations, nonproteolytic/cryo-activation of prorenin, pH of the reaction, incubation temperature/time, angiotensin I degradation by peptidases, etc.) produce considerably variable results in PRA determinations 2, 7, 10, 13, 16, 17, 18, 19, 20, 21.
Recently, immunoradiometric assays (IRMA) for the direct measurement of renin (EC 3.4.99.19) have been developed 7, 12, 19, 22, 23, 24, 25. Two of these assays are commercially available. Renin, which is produced intracellularly in the kidney 26, 27from enzymatically inactive prorenin and then released into the circulation by regulated secretion 2, 7, 27, 28(constituting 10–20% of total circulating renin7, 29), usually represents the activation of the renin–angiotensin system as precisely as PRA, because it is the rate-limiting enzyme for angiotensin II formation in plasma 2, 27, 28. During childhood, the indications for renin measurement are the same as in adults, whereas prorenin was recently found to be an important marker in nephroblastoma and for prediction of microvascular complications in diabetes mellitus 30, 31. As there exists virtually no experience with this method in the childhood age group [10], we determined serum renin concentrations in 281 healthy children in order to provide reference data for future studies.
Section snippets
Subjects
A group of 281 healthy children (177 males; 104 females), aged 0–18 years, were enrolled in our study. For ethical reasons, we employed only surplus sera (no plasma) from our laboratory, taken for otherwise necessary investigations. Other physicians were not aware of the ongoing study to avoid involuntary help by drawing additional amounts of blood. We retraced the records of the corresponding children and included them in our study if they fulfilled the following criteria: the children were in
Results
There was a significant difference between renin concentrations in umbilical cord compared to newborn infants (first week of life) (P<0.005) and the older age groups (P<0.002) (Table 1). Newborn infants during the first week showed higher concentrations than older children, but this only reached statistical significance in comparison with certain age groups, e.g. 7 years and older (P<0.05). The same results were obtained for infants 4 months–1 year old and children 5–7 years old compared to
Discussion
Although the determination of PRA is well established in clinical medicine, there are drawbacks to this method (which apply also to the enzyme kinetic PRC assay) 2, 7, 13, 16, 19, 20. The results depend on the enzyme (renin) and substrate (angiotensinogen) concentrations, therefore the measurement of the in vitro generated angiotensin I is only an estimate of the real renin concentration. Serious over- or underestimations can occur 2, 7, 11, 12, 13, 14, 15, 16, 19, 20, 23, 24, 29, 38. A
Acknowledgements
We thank Mrs. Jutta Biskupek-Sigwart and Mrs. Ulrike Blum for expert technical assistance. Further, we are grateful to Dr. Peter Haima, Nichols Institute Diagnostic, Netherlands, who provided us with information about correlation of PRA and immunoreactive renin as well as plasma and serum renin concentration.
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- 1
Parts of the results were presented at the 90th Annual Meeting of the Deutsche Gesellschaft für Kinderheilkunde, Hannover, Germany, 18–21 September 1994.