Kidney denervation prior to brain death does not prevent brain death-induced kidney injury

Background:
Brain death (BD) negatively impacts transplant outcomes. Still, the pathophysiology of kidney damage
caused by BD is poorly understood, especially concerning the contribution of the sympathetic nervous
system. We aim at investigating whether renal denervation (DNRV) performed prior to BD induction
attenuates kidney injury.
Methods:
Renal denervation (DNRV) was performed on the left kidney of rats using a method adapted from
Eriguchi and Tsuruya. This procedure involved the dissection of renal nerve fibers and the application
of 10% phenol in ethanol to the renal artery. BD was induced via intracranial pressure elevation using a
Fogarty catheter. BD was confirmed by the absence of pupillary reflexes, a positive apnea test, and a
Cushing reflex. Kidney norepinephrine (NE) levels, tubular damage (extent of acute tubular necrosis -
ATN), and kidney injury biomarkers (Casp3, Ki67, KIM1) were compared to the paired contralateral
non-denervated kidney (CTL).
Additionally, kidney samples were subjected to high-throughput RNA sequencing (Illumina®). Paired
differential expression analysis followed by pathway enrichment analysis were performed using
DESeq2 in R and IPA (Qiagen®), respectively.
Results:
Renal denervation effectively reduced kidney NE levels 6h post BD (DNRV: 1.64 pg/mL [1.44–2.01]
vs. CTL: 2.16 pg/mL [1.81–2.79], p = 0.0312, confirming the suppression of sympathetic input. No
significant differences were observed in ATN extent (DNRV: 50% [25–55] vs. CTL: 60% [45–70], p =
0.13), serum creatinine increase (DNRV: +0.040 ± 0.011 mg/dL/h vs. CTL: 0.053 ± 0.022 mg/dL/h, p
= 0.13), or expression of injury biomarkers. RNA sequencing data detected no significant differences
between DNRV and CTL kidneys.
Conclusions:
Although renal denervation effectively reduced the sympathetic input, it did not prevent BD-induced
kidney injury in our rat model. These findings suggest that neurogenic mechanisms play a limited role
in BD-associated kidney damage.