Differential associations between kidney and vascular health biomarkers in young adults stratified by blood pressure status: The African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension study.

Abstract

Objective: Hypertension and kidney disease share common pathophysiological pathways involved in endothelial dysfunction including increased oxidative stress and chronic inflammation. The precise early-stage mechanisms associated with nephron-specific kidney injury remain unclear. We aimed to explore associations of kidney function biomarkers with markers representing these mechanisms in young adults stratified by blood pressure status [according to 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines].

Methods: We cross-sectionally analysed 1055 adults. Kidney biomarkers included estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (uACR), alpha-1 microglobulin (uA1M), neutrophil gelatinase-associated lipocalin (uNGAL), uromodulin (uUMOD) and CKD273 classifier. Markers of oxidative stress [gamma-glutamyl transferase (GGT); malondialdehyde (MDA)], inflammation [interleukin 6 (IL-6); C-reactive protein (CRP); fibrinogen] and endothelial function [soluble intercellular adhesion molecule-1; soluble vascular cell adhesion molecule-1 (sVCAM-1); von Willebrand factor antigen (vWFag); monocyte chemoattractant protein-1 (MCP-1); plasminogen activator inhibitor-1 activity (PAI-1act); urinary nitrate-to-nitrite ratio] were analysed.

Results: Individuals in the hypertensive group (mean age 24.8 years; 73.2% men; 39% Black) had higher GGT, CRP, IL-6, MCP-1 and PAI-1act levels (all P ≤ 0.024) compared to their normotensive counterparts. In individuals with hypertension, eGFR associated negatively and uNGAL positively with IL-6, while uA1M associated positively with PAI-1act (all P ≤ 0.047). In the same group, UMOD associated positively with fibrinogen and CKD273 classifier negatively with MCP-1 (all P ≤ 0.021). In contrast, eGFR associated positively with MDA and negatively with GGT, CKD273 classifier associated positively with GGT, sVCAM-1 and vWFag, and uACR associated negatively with CRP (all P ≤ 0.033) in normotensives.

Conclusion: In young adults, mechanisms linked to early nephron-specific kidney injury biomarkers differ according to blood pressure status.