A systematic review of the measurement of the renin-angiotensin and kallikrein-kinin system peptides in normotension and hypertension.

Authors

Elliot J Gyedu, Sian Jenkins, Dan Lane, Ammar Akram, Farah Salim, Leong L Ng, Donald J L Jones, Dennis Bernieh, Pankaj Gupta

Published in

Journal of human hypertension. Jul 30, 2026. Epub Jul 30, 2026.

Abstract

Hypertension is the leading modifiable risk factor for cardiovascular diseases and affects over 1.3 billion adults. The renin-angiotensin and kallikrein-kinin systems (RAS and KKS) are critical in regulating blood pressure (BP). Clinically, the RAS and KKS have gained renewed importance, especially due to the discovery of the non-canonical vasodilative RAS pathway. Thus, for their clinical use, clarity on their measurement and reference ranges is essential. This systematic review aimed to synthesise the reported baseline circulating concentrations of RAS and KKS peptides, and the pre-analytical and analytical methods used in measuing them, in normotensive and untreated hypertensive adults. It adhered to PRISMA guidelines and synthesised data from 27 of 2864 retrieved studies that met the inclusion criteria. Reported peptide concentrations varied widely, ranging from 0.06-81.85 × 10³ fmol/mL. However, there was substantial heterogeneity across included studies in sample collection procedures, protease inhibitor use for peptide stabilisation, participant clinical phenotyping, BP reporting, and analytical methods. Reported levels of several RAS and KKS peptides were generally lower in hypertensive cohorts than in normotensive cohorts; however, these differences should be interpreted cautiously given the small number of hypertensive studies, incomplete BP reporting, and substantial heterogeneity across all included studies. Current evidence is insufficient to establish reference ranges for RAS and KKS peptides. This review emphasises the need for standardisation of sampling protocols, comprehensive peptide stabilisation, consistent clinical phenotyping, and robust analytical methods before RAS and KKS peptides can be used as clinical markers and their therapeutic potential identified.

PMID:
42533027
Bibliographic data and abstract were imported from PubMed on 31 Jul 2026.

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