Why is diabetes mellitus a risk factor for contrast-induced nephropathy?

Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute kidney injury, as the usage of contrast media for imaging and intravascular intervention keeps expanding. Diabetes is an important predisposing factor for CIN, particularly in patients with renal functional impairment. Renal hypoxia, combined with the generation of reactive oxygen species, plays a central role in the pathogenesis of CIN, and the diabetic kidney is particularly susceptible to intensified hypoxic and oxidative stress following the administration of contrast media.

Reactive oxygen species and the pathogenesis of radiocontrast-induced nephropathy.

Experimental findings in vitro and in vivo illustrate enhanced hypoxia and the formation of reactive oxygen species (ROS) within the kidney following the administration of iodinated contrast media, which may play a role in the development of contrast media-induced nephropathy. Clinical studies indeed support this possibility, suggesting a protective effect of ROS scavenging or reduced ROS formation with the administration of N-acetyl cysteine and bicarbonate infusion, respectively. Furthermore, most risk factors, predisposing to contrast-induced nephropathy are prone to enhanced renal parenchymal hypoxia and ROS formation.

Experimental ischemia-reperfusion: biases and myths-the proximal vs. distal hypoxic tubular injury debate revisited.

Although the understanding of processes associated with hypoxic tubular cell injury has remarkably improved, controversies remain regarding the appropriateness of various animal models to the human syndrome of acute kidney injury (AKI). We herein compare available experimental models of hypoxic acute kidney damage, which differ both conceptually and morphologically in the distribution of tubular cell injury. Tubular segment types differ in their capacity to mount hypoxia-adaptive responses, mediated by hypoxia-inducible factors (HIFs), and in cell type-specific molecules shed into the urine, which may serve as early biomarkers for renal damage.

Animal models of renal dysfunction: acute kidney injury.

Background: Acute renal failure (ARF) is a broad clinical entity, encompassing diverse pathophysiologies, with heterogeneous functional and morphological features. In the same fashion, various animal models of ARF differ in their mechanisms, distribution and type of injury, cellular responses and outcome.

Objective: To appraise available animal models of ARF used for the assessment of potential therapeutic interventions, providing their basic pathophysiologies.

N-acetylcysteine ameliorates renal microcirculation: studies in rats.

Background: N-acetylcysteine (NAC) administration has been shown to ameliorate experimental acute renal failure induced by ischemia-reflow, and was found to prevent radiocontrast nephropathy in high-risk patients. While the protective effect of NAC has been primarily attributed to scavenging oxygen free radicals, improving renal microcirculation also may play a role in the prevention of acute renal failure.

Methods: This study was designed to explore the effect of NAC on renal microcirculation.

Proximal tubular injury attenuates outer medullary hypoxic damage: studies in perfused rat kidneys.

The straight segment (S3) of the proximal tubule is predominantly damaged during renal ischemia-reflow, whereas medullary thick ascending limbs (mTALs) are principally affected in other models of hypoxic acute tubular necrosis (ATN). Since the latter injury pattern largely depends on the extent of reabsorptive activity during hypoxic stress, we hypothesized that proximal tubular damage might attenuate downstream mTAL injury by means of diminished distal solute delivery for reabsorption. In isolated rat kidneys perfused for 90 min with oxygenated Krebs-Henseleit solution, mTAL necrosis developed in 75 +/- 3% of tubules in the mid-inner stripe of the outer medulla.

Tissue oxygenation modifies nitric oxide bioavailability.

Objective: Because changes in blood oxygenation acutely alter vascular tone, we explored a possible modulation of nitric oxide-induced vasodilation (nitrovasodilation) by oxygen.

Methods: We studied the effects of manipulation of tissue oxygenation on renal parenchymal nitric oxide (NO) with a selective NO electrode placed in the well-oxygenated renal cortex or in the physiologically hypoxemic outer medulla.

Results: In the cortex, as expected, NO signals fell in response to the NO synthase (NOS) inhibitor L-NAME.