Metabolomics of renal venous plasma from individuals with unilateral renal artery stenosis and essential hypertension

Objective: To compare the metabolite profiles of venous effluent from both kidneys of individuals with unilateral atherosclerotic renal artery stenosis (ARAS) in order to directly examine how impaired renal blood flow impacts small-molecule handling in humans. Methods: We applied liquid chromatography-mass spectrometry based metabolite profiling to venous plasma obtained from the stenotic (STK) and contralateral (CLK) kidneys of ARAS patients (n=16), and both the kidneys of essential hypertensive controls (n=11). Study samples were acquired during a 3-day protocol that included iothalamate clearance measurements, radiographic kidney phenotyping (Duplex ultrasound, multidetector computed tomography, and blood-oxygen-level-dependent MRI), and controlled sodium and caloric intake and antihypertensive treatment. Results: Partial least squares-discriminant analysis demonstrated clear separation of essential hypertensive kidney metabolite profiles versus STK and CLK metabolite profiles, but no separation between metabolite profiles of STK and CLK samples. All of the discriminating metabolites were similarly elevated in the STK and CLK samples, likely reflecting the lower glomerular filtration rate in the ARAS versus essential hypertensive individuals (mean 66.1 versus 89.2 ml/min per 1.73m2). In a paired analysis within the ARAS group, no metabolite was significantly altered in STK compared with CLK samples; notably, creatinine was the same in STK and CLK samples (STK/CLK ratio=1.0, P=0.9). Results were unchanged in an examination of ARAS patients in the bottom half of renal tissue perfusion or oxygenation. Conclusion: Metabolite profiling does not differentiate venous effluent from STKs or CLKs in individuals with unilateral ARAS, despite the measurable loss of kidney volume and blood flow on the affected side. These findings are consistent with the kidney's ability to adapt to ARAS to maintain a range of metabolic functions.