Levels of angiotensin peptides in healthy and cardiovascular/renal-diseased paediatric population—an investigative review

Abstract

The renin-angiotensin-aldosterone system (RAAS) plays a major role in the regulation of blood pressure and homeostasis. Therefore, it is a commonly used target for pharmacotherapy of cardiovascular diseases in adults. However, the efficacy of this pharmacotherapy can only be limitedly derived into children. Comprehensive knowledge of the humoral parameters acting in the paediatric RAAS (e.g. angiotensin I, angiotensin II, angiotensin 1–7, angiotensin III, and angiotensin IV) might facilitate a more effective and rational pharmacotherapy in children. Therefore, this review aims to provide an overview of the maturing RAAS. Out of 925 identified records, 35 publications were classified as relevant. Physiological and pathophysiological concentrations of angiotensin peptides were compiled and categorised according to European Medicines Agency age groups. Age has a major impact on circulating angiotensin I, angiotensin II, and angiotensin 1–7, which is reflected in an age-dependent decrease during childhood. In contrast to data obtained in adults, no gender-related differences in angiotensin levels were identified. The observed increase in peptide concentrations regarding cardiac- and renal-diseased children is influenced by surgical repair, while evidence for a pharmacological impact is conflicting. A comprehensive set of angiotensin I, angiotensin II, and angiotensin 1–7 values from neonates up to adolescents was compiled. Indicating age as a strong effector. However, evidence about potential promising targets of the RAAS like angiotensin III and angiotensin IV is still lacking in children.

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Abbreviations

ACEi:

Angiotensin-converting enzyme inhibitor

AGA:

Appropriate for gestational age

ANCS:

Antenatal corticosteroids

Ang:

Angiotensin

ASD:

Atrial septal defect

BDG:

Bidirectional Glenn

CCB:

Calcium channel blocker

CRF:

Chronic renal failure

CVD:

Cardiovascular disease

ELISA:

Enzyme-linked immunosorbent assay

EMA:

European Medicines Agency

ESRD:

End-stage renal disease

GA:

Gestational age

HPLC:

High-pressure liquid chromatography

HUT:

Head-up tilt

IQR:

Interquartile range

LENA:

Labeling of enalapril up to adolescents

MLBW:

Moderate-low birthweight

NBW:

Normal birthweight

RAAS:

Renin-angiotensin-aldosterone system

RF:

Renal failure

RIA:

Radioimmunoassay

SD:

Standard deviation

SE:

Standard error

SGA:

Small for gestational age

SRINS:

Steroid-resistant idiopathic nephrotic syndrome

UV/VIS:

Ultraviolet/visible spectroscopy

VLBW:

Very low birthweight

VSD:

Ventricular septal defect

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Acknowledgements

We thank Jutta Tins for the assistance in double-checking the data and Prof. Dr. Stephanie Laeer for conceptual support.

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Conception and design of the work were developed in close collaboration by Suessenbach FK and Burckhardt BB. Data collection and analysis were performed by Suessenbach FK. The interpretation and drafting of the article were done by Suessenbach FK and Burckhardt BB. Critical revision and final approval of the version to be published were given by Burckhardt BB.

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Correspondence to B. B. Burckhardt.

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Suessenbach, F.K., Burckhardt, B.B. Levels of angiotensin peptides in healthy and cardiovascular/renal-diseased paediatric population—an investigative review. Heart Fail Rev 24, 709–723 (2019). https://doi.org/10.1007/s10741-019-09797-y

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Keywords

  • RAAS
  • Angiotensin
  • Paediatric
  • Cardiovascular disease
  • Renal disease