Pathophysiology of Radiocontrast Nephropathy

Abstract

Recent experimental data underlies the role of hypoxic tubular injury in the pathophysiology of radiocontrast nephropathy. Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-hemoglobin dissociation curve may all contribute to intrarenal hypoxia, imbalance between oxygen demand and supply plays a major role in radiocontrast-induced outer medullary hypoxic damage. Low oxygen tension normally exists in this renal region, reflecting the precarious regional oxygen supply and a high local metabolic rate and oxygen requirement, resulting from active salt reabsorption by medullary thick ascending limbs of Henle's loop. Radiologic contrast agents markedly aggravate outer medullary physiologic hypoxia. This results from enhanced metabolic activity and oxygen consumption (as a result of osmotic diuresis and increased salt delivery to the distal nephron) because the regional blood flow and the oxygen supply actually increase. The latter effect may result in part from the activation of various regulatory mediators of outer medullary blood flow to ensure maximal regional oxygen supply. Low-osmolar radiocontrast agents may be less nephrotoxic because of the smaller osmotic load and vasomotor alterations. Experimental radiocontrast-induced renal failure requires preconditioning of animals with various insults (for example, congestive heart failure, reduced renal mass, salt depletion, or inhibition of nitric oxide and prostaglandin synthesis). In all these perturbations, which resemble clinical conditions that predispose to contrast nephropathy, outer medullary hypoxic injury results from insufficiency or inactivation of mechanisms designed to preserve regional oxygen balance. This underlines the importance of identifying and ameliorating predisposing factors in the prevention of this iatrogenic disease.

Regional decreases in renal oxygenation during graded acute renal arterial stenosis: a case for renal ischemia

“…This is in agreement with clinical observations of medullary vulnerability to abrupt decreases in renal perfusion. (4,5,23) Hypoxia occurs despite the lack of an overall O 2 delivery and consumption mismatch, thus implying that global measures of renal hemodynamics are insufficient to fully explain regional differences.…”

Gadolinium contrast media are more nephrotoxic than a low osmolar iodine medium employing doses with equal x-ray attenuation in renal arteriography: An experimental study in pigs1

“…All hypertonic solutions significantly increased elimination half-life, increasing with the osmolality of the agents. Apart from the direct exposure of red blood cells, endothelial cells, and tubular cells to the hypertonic solutions injected into the renal artery, the CM also represent an osmotic load to the kidneys with secondary diuresis and natriuresis (1,55,56). Osmotic load may activate the tubuloglomerular feedback mechanism mediating vasoconstrictive agents, increase medullary oxygen demand for active reabsorption of the increased tubular sodium load resulting in hypoxic injuries, or increase intratubular pressure with elevation of interstitial pressure and secondary vascular compression beneath the rigid renal capsula.…”

Contrast‐induced nephropathy

“…Thus far, several pathophysiological mechanisms of CIN have been proposed, including direct toxicity to renal tubular epithelium, oxidative stress, ischemic injury, and tubular obstruction [6,7]. Low blood flow in the medulla leading to medullary hypoxia might result from increased perivascular hydrostatic pressure, increased intratubular pressure secondary to contrastinduced diuresis, vasoconstriction due to redundance of vasoactive substances as adenosin and endothelin, and decrease of nitric oxide and prostaglandins [8,9]. Excretion of the contrast medium requires significant urine volume to clear the osmotic load.…”