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Urinary albumin-to-creatinine ratio is inversely related to nitric oxide synthesis in young black adults: the African-PREDICT study

Abstract

Hypertension is common in black populations and is known to be associated with low nitric oxide (NO) bioavailability. We compared plasma and urinary NO-related markers and plasma creatine kinase (CK) levels between young healthy black and white adults along with the associations of these markers with the urinary albumin-to-creatinine ratio (uACR), which is a surrogate marker of endothelial and kidney function. We included 1105 participants (20–30 years). We measured the uACR, plasma CK, plasma and urinary arginine, homoarginine, asymmetric (ADMA) and symmetric dimethylarginine (SDMA), urinary ornithine/citrulline, nitrate and nitrite, and malondialdehyde (MDA). In addition, the urinary nitrate-to-nitrite ratio (UNOxR) was calculated and used as a measure of circulating NO bioavailability. The uACR was comparable between the groups, yet the black group had lower urinary nitrate (by −15%) and UNOxR values (by −18%) (both p ≤ 0.001), higher plasma (by +9.6%) and urinary (by +5.9%) arginine (both p ≤ 0.004), higher plasma (by +13%) and urinary (by +3.7%) ADMA (both p ≤ 0.033), and higher CK (by +9.5%) and MDA (by +19%) (both p < 0.001) compared with white adults. Plasma and urinary homoarginine were similar between the groups. In the multiple regression analysis, we confirmed the inverse associations of the uACR with both plasma (adj. R2 = 0.066; β = −0.209; p = 0.005) and urinary (adj. R2 = 0.066; β = −0.149; p = 0.010) homoarginine and with the UNOxR (adj. R2 = 0.060; β = −0.122; p = 0.031) in the black group only. The overall less favorable NO profile and higher CK and MDA levels in the black cohort along with the adverse associations with the uACR may reflect the vulnerability of this cohort to the early development of hypertension.

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Acknowledgements

The authors are grateful to all individuals who participated voluntarily in the African-PREDICT study. The dedication of the support and research staff as well as the students at the Hypertension Research and Training Clinic at the North-West University (Potchefstroom campus) are also duly acknowledged.

Funding

The research funded in this manuscript is part of an ongoing research project financially supported by the South African Medical Research Council (SAMRC) with funds from the National Treasury under the Economic Competitiveness and Support Package; the South African Research Chairs Initiative (SARChI) of the Department of Science and Technology and National Research Foundation (NRF) of South Africa (GUN 86895); SAMRC with funds received from the South African National Department of Health, GlaxoSmithKline R&D (Africa Non-Communicable Disease Open Lab grant), the UK Medical Research Council with funds from the UK Government’s Newton Fund; and corporate social investment grants from Pfizer (South Africa), Boehringer-Ingelheim (South Africa), Novartis (South Africa), the Medi Clinic Hospital (South Africa), and kind contributions from the Roche Group (South Africa). Any opinions, findings, conclusions, or recommendations expressed in this material are those of the authors, and therefore, the NRF does not accept any liability in this regard.

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Correspondence to Ruan Kruger.

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Craig, A., Mels, C.M.C., Schutte, A.E. et al. Urinary albumin-to-creatinine ratio is inversely related to nitric oxide synthesis in young black adults: the African-PREDICT study. Hypertens Res 44, 71–79 (2021). https://doi.org/10.1038/s41440-020-0514-1

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Keywords

  • Urinary albumin-to-creatinine ratio
  • Nitric oxide
  • Homoarginine
  • Urinary nitrate-to-nitrite ratio
  • Hypertension

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