Renal Parenchymal hypoxia, hypoxia adaptation, and the pathogenesis of radiocontrast nephropathy

Background and objectives: Renal parenchymal P-O2 declines after the administration of iodinated radiocontrast agents, reaching critically low levels of approximately 10 mmHg in medullary structures. Design, setting, participants, & measurements: In this review, the causes of renal parenchymal hypoxia and its potential role in the pathogenesis of contrast nephropathy are appraised. Results: Commonly associated predisposing factors are associated with a propensity to enhance renal hypoxia. Indeed, animal models of radiocontrast nephropathy require the induction of such predisposing factors, mimicking clinical scenarios that lead to contrast nephropathy in high-risk individuals. In these models, in association with medullary hypoxic damage, a transient local cellular hypoxia response is noted, initiated at least in part by hypoxia-inducible factors. Some predisposing conditions that are distinguished by chronically aggravated medullary hypoxia, such as tubulointerstitial disease and diabetes, are characterized by a priori upregulation of hypoxia-inducible factors, which seems to confer tolerance against radiocontrastrelated hypoxic tubular damage. Renal dysfunction under such circumstances likely reflects to some extent altered intrarenal hemodynamics, rather than acute tubular injury. Conclusions: Real-time, noninvasive novel methods may help to differentiate between evolving tubular damage and altered hemodynamics and in the design of appropriate preventive interventions.