Pathophysiology of radiocontrast nephropathy - A role for medullary hypoxia

Recent experimental data underlies the role of hypoxic tubular injury in th e pathophysiology of radiocontrast nephropathy, Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-h emoglobin dissociation curve may all contribute to intrarenal hypoxia, imba lance 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 pre carious regional oxygen supply and a high local metabolic rate and oxygen r equirement, resulting from active salt reabsorption by medullary thick asce nding limbs of Henle's loop. Radiologic contrast agents markedly aggravate outer medullary physiologic hypoxia, This results from enhanced metabolic a ctivity and oxygen consumption (as a result of osmotic diuresis and increas ed 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 bloo d flow to ensure maximal regional oxygen supply. Low-osmolar radiocontrast agents may be less nephrotoxic because of the smaller osmotic load and vaso motor alterations. Experimental radiocontrast-induced renal failure requires preconditioning o f animals with various insults (for example, congestive heart failure, redu ced renal mass, salt depletion, or inhibition of nitric oxide and prostagla ndin synthesis). In all these perturbations, which resemble clinical condit ions that predispose to contrast nephropathy, outer medullary hypoxic injur y results from insufficiency or inactivation of mechanisms designed to pres erve regional oxygen balance. This underlines the importance of identifying and ameliorating predisposing factors in the prevention of this iatrogenic disease.