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March 1, 2005Journal of Clinical Investigation

Arterial and renal consequences of partial genetic deficiency in tissue kallikrein activity in humans

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Why the study?

Does partial genetic deficiency in tissue kallikrein activity (R53H polymorphism) affect vascular, hormonal, and renal phenotypes in young normotensive males under varying dietary sodium and potassium conditions?

Population

40 young normotensive white males (30 R53R-homozygous and 10 R53H-heterozygous for the tissue kallikrein gene)

Comparison

Low sodium-high potassium diet and high… vs Crossover design comparing the two diets, as…

Design

RCT, Randomly assigned to receive both diets in a crossover design

Follow-up

2 weeks (1 week per diet)

Authors

MAMichel AziziPBPierre BoutouyrieABAlvine Bissery

Discussion

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Overview

R53H carriers may face elevated long-term vascular risk despite normotension; extends tissue kallikrein’s role to human arterial structure.

Structured PICO

Does partial genetic deficiency in tissue kallikrein activity (R53H polymorphism) affect vascular, hormonal, and renal phenotypes in young normotensive males under varying dietary sodium and potassium conditions?

P
Population
40 young normotensive white males (30 R53R-homozygous and 10 R53H-heterozygous for the tissue kallikrein gene)
I
Intervention
Low sodium-high potassium diet (to stimulate tissue kallikrein synthesis) and high sodium-low potassium diet (to suppress tissue kallikrein synthesis), each for 1 week
C
Comparator
Crossover design comparing the two diets, as well as comparing R53H-heterozygous subjects to R53R-homozygous subjects
O
Outcome
Vascular, hormonal, and renal phenotypes (including urinary kallikrein activity, brachial artery vasodilatation, wall shear stress, and artery diameter)surrogate

Partial genetic deficiency in tissue kallikrein activity is associated with inward remodeling of the brachial artery and increased wall shear stress, representing a novel form of arterial dysfunction.

Cite This Study

Azizi et al. (2005) studied this question.

synapsesocial.com/papers/6a8491bb20d7d47bbaf795e5https://doi.org/10.1172/jci200523669
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Loss-of-Function Polymorphism of the Human Kallikrein Gene with Reduced Urinary Kallikrein Activity2002 · 72 citations
  2. 2Reduced activity of the kallikrein–kinin system predominates over renin–angiotensin system overactivity in all conditions of sodium balance in essential hypertensives and family-related hypertension2003 · 7 citations
  3. 3Urinary kallikrein and plasma renin activity as determinants of renal blood flow. The influence of race and dietary sodium intake.1977 · 223 citations
  4. 4Kallikreins and Kinins1995 · 115 citations
  5. 5ACE Genotype and Endothelium-Dependent Vasodilation of Conduit Arteries and Forearm Microcirculation in Humans2001 · 25 citations