Abstract: Acute kidney injury (AKI) is one of the main complications in
acute care medicine and a risk factor for chronic kidney disease
(CKD). AKI incidence has increased; however, its diagnosis
has limitations and physiopathological mechanisms are
underexplored. We investigated urine samples, aiming to
identify major metabolite changes during human AKI evolution.
Metabolic signatures found were further explored for a
potential link to severity of injury. Twenty-four control subjects
and 38 hospitalized patients with AKI were recruited and
urine samples were collected at the time of diagnosis, during
follow-up and at discharge. Nuclear magnetic resonance
(NMR) was used in a first discovery phase for identifying potential
metabolic differences. Target metabolites of interest were
confirmed by liquid chromatography-mass spectrometry (LCMS/
MS) in an independent group. Underlying metabolic defects
were further explored by kidney transcriptomics of murine toxic
AKI. Urinary 2-hydroxybutyric acid, pantothenic acid, and
hippuric acid were significantly downregulated and urinary Nacetylneuraminic
acid, phosphoethanolamine, and serine were
upregulated during AKI. Hippuric acid, phosphoethanolamine,
and serine showed further downregulation/upregulation depending
on the metabolite in acute tubular necrosis (ATN) AKI compared
to prerenal AKI. Kidney transcriptomics disclosed decreased
expression of cystathionase, cystathionine-?-synthase,
and ethanolamine-phosphate cytidylyltransferase, and increased
N-acetylneuraminate synthase as the potentially underlying
cause of changes in urinary metabolites. A urinary metabolite
panel identifiedAKI patients and provided insight into intrarenal
events. A urine fingerprint made up of six metabolites may be
related to pathophysiological changes in oxidative stress, energy
generation, and H2S availability associated with AKI.
